Difference between revisions of "Recurrent Genomic Alterations in Pediatric and Adult Central Nervous System Tumors Detected by Chromosomal Microarray"
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'''Recurrent Genomic Alterations in Pediatric and Adult Central Nervous System Tumors Detected by Chromosomal Microarray''' | '''Recurrent Genomic Alterations in Pediatric and Adult Central Nervous System Tumors Detected by Chromosomal Microarray''' | ||
| − | '''Table 1:''' Pediatric CNS Tumors. | + | '''Table 1:''' Pediatric CNS Tumors. CGC CNS Workgroup 2015-2018. Table derived from Neill et al., 2020 [[https://pubmed.ncbi.nlm.nih.gov/32203924/ PMID: 32203924]] with permission from Cancer Genetics. |
{| class="wikitable" | {| class="wikitable" | ||
|- | |- | ||
| − | ! TUMOR | + | !TUMOR |
| − | ! SUBTYPES | + | !SUBTYPES |
| − | ! BROAD ABERRATIONS (>10Mb) | + | !BROAD ABERRATIONS (>10Mb) |
| − | ! FOCAL ABERRATIONS (<10Mb) | + | !FOCAL ABERRATIONS (<10Mb) |
| − | ! CLINICAL FEATURES | + | !CLINICAL FEATURES |
| − | ! REFERENCES | + | !REFERENCES |
|- | |- | ||
|'''GLIOMAS''' | |'''GLIOMAS''' | ||
| Line 18: | Line 18: | ||
|WHO CNS Tumors (2016) | |WHO CNS Tumors (2016) | ||
|- | |- | ||
| − | | Low grade glioma, WHO grade I | + | |Low grade glioma, WHO grade I |
| − | | Pilocytic astrocytoma/pilomyxoid astrocytoma | + | |Pilocytic astrocytoma/pilomyxoid astrocytoma |
| − | | Some tumors show polysomy 7; other polysomies more common in adult PA | + | |Some tumors show polysomy 7; other polysomies more common in adult PA |
| − | | '''Fusions:''' KIAA1549-BRAF fusion (via 3'BRAF duplication), other BRAF partners reported; NTRK fusions (rare); FGFR1 fusions (rare) <br> | + | |'''Fusions:''' [[KIAA1549]]-[[BRAF]] fusion (via 3'[[BRAF]] duplication), other [[BRAF]] partners reported; NTRK fusions (rare); [[FGFR1]] fusions (rare) <br> |
| − | '''Mutations:''' BRAF V600E (particularly extra-cerebellar tumors); FGFR1 (midline PA); NF1 (esp. germline), other MAPK pathway mutations <br> | + | '''Mutations:''' [[BRAF]] V600E (particularly extra-cerebellar tumors); [[FGFR1]] (midline PA); [[NF1]] (esp. germline), other MAPK pathway mutations <br> |
| − | '''Loss:''' NF1 in optic pathway PA | + | '''Loss:''' [[NF1]] in optic pathway PA |
| − | | Classic PA are cerebellar (most commonly associated with BRAF duplication); PA in patients with germline NF1 alterations often develop as optic gliomas;Surgical resection can be curative; PMA generally more aggressive than PA; BRAF fusions and BRAF mutations generally are mutually exclusive | + | |Classic PA are cerebellar (most commonly associated with BRAF duplication); PA in patients with germline NF1 alterations often develop as optic gliomas;Surgical resection can be curative; PMA generally more aggressive than PA; BRAF fusions and BRAF mutations generally are mutually exclusive |
| − | | PMID:19016743; PMCID:2761618; PMID:18716556 PMID:25461780 PMID:25664944; PMID:26378811 PMCID:3429698; PMID:23817572; PMID:23583981 PMID:18974108; PMID:23278243; PMID:21274720 | + | |<ref>{{Cite journal|last=Sievert|first=Angela J.|last2=Jackson|first2=Eric M.|last3=Gai|first3=Xiaowu|last4=Hakonarson|first4=Hakon|last5=Judkins|first5=Alexander R.|last6=Resnick|first6=Adam C.|last7=Sutton|first7=Leslie N.|last8=Storm|first8=Phillip B.|last9=Shaikh|first9=Tamim H.|date=2009-07|title=Duplication of 7q34 in pediatric low-grade astrocytomas detected by high-density single-nucleotide polymorphism-based genotype arrays results in a novel BRAF fusion gene|url=https://pubmed.ncbi.nlm.nih.gov/19016743|journal=Brain Pathology (Zurich, Switzerland)|volume=19|issue=3|pages=449–458|doi=10.1111/j.1750-3639.2008.00225.x|issn=1750-3639|pmc=2850204|pmid=19016743}}</ref>PMID:19016743; <ref>{{Cite journal|last=Jones|first=David T. W.|last2=Ichimura|first2=Koichi|last3=Liu|first3=Lu|last4=Pearson|first4=Danita M.|last5=Plant|first5=Karen|last6=Collins|first6=V. Peter|date=2006-11|title=Genomic Analysis of Pilocytic Astrocytomas at 0.97 Mb Resolution Shows an Increasing Tendency Toward Chromosomal Copy Number Change With Age|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761618/|journal=Journal of neuropathology and experimental neurology|volume=65|issue=11|pages=1049–1058|doi=10.1097/01.jnen.0000240465.33628.87|issn=0022-3069|pmc=2761618|pmid=17086101}}</ref>PMCID:2761618; <ref>{{Cite journal|last=Bar|first=Eli E.|last2=Lin|first2=Alex|last3=Tihan|first3=Tarik|last4=Burger|first4=Peter C.|last5=Eberhart|first5=Charles G.|date=2008-09|title=Frequent gains at chromosome 7q34 involving BRAF in pilocytic astrocytoma|url=https://pubmed.ncbi.nlm.nih.gov/18716556|journal=Journal of Neuropathology and Experimental Neurology|volume=67|issue=9|pages=878–887|doi=10.1097/NEN.0b013e3181845622|issn=0022-3069|pmid=18716556}}</ref>PMID:18716556 <ref name=":0">{{Cite journal|last=Appin|first=Christina L.|last2=Brat|first2=Daniel J.|date=2015-01|title=Molecular pathways in gliomagenesis and their relevance to neuropathologic diagnosis|url=https://pubmed.ncbi.nlm.nih.gov/25461780|journal=Advances in Anatomic Pathology|volume=22|issue=1|pages=50–58|doi=10.1097/PAP.0000000000000048|issn=1533-4031|pmid=25461780}}</ref>PMID:25461780 <ref name=":1">{{Cite journal|last=Venneti|first=Sriram|last2=Huse|first2=Jason T.|date=2015-03|title=The evolving molecular genetics of low-grade glioma|url=https://pubmed.ncbi.nlm.nih.gov/25664944|journal=Advances in Anatomic Pathology|volume=22|issue=2|pages=94–101|doi=10.1097/PAP.0000000000000049|issn=1533-4031|pmc=4667550|pmid=25664944}}</ref>PMID:25664944; <ref name=":2">{{Cite journal|last=Fontebasso|first=Adam M.|last2=Shirinian|first2=Margret|last3=Khuong-Quang|first3=Dong-Anh|last4=Bechet|first4=Denise|last5=Gayden|first5=Tenzin|last6=Kool|first6=Marcel|last7=De Jay|first7=Nicolas|last8=Jacob|first8=Karine|last9=Gerges|first9=Noha|date=2015-10-13|title=Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age|url=https://pubmed.ncbi.nlm.nih.gov/26378811|journal=Oncotarget|volume=6|issue=31|pages=31844–31856|doi=10.18632/oncotarget.5571|issn=1949-2553|pmc=4741644|pmid=26378811}}</ref>PMID:26378811 <ref>{{Cite journal|last=Rodriguez|first=Fausto J.|last2=Ligon|first2=Azra H.|last3=Horkayne-Szakaly|first3=Iren|last4=Rushing|first4=Elisabeth J.|last5=Ligon|first5=Keith L.|last6=Vena|first6=Natalie|last7=Garcia|first7=Denise I.|last8=Cameron|first8=J. Douglas|last9=Eberhart|first9=Charles G.|date=2012-9|title=BRAF Duplications and MAPK Pathway Activation Are Frequent in Gliomas of the Optic Nerve Proper|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429698/|journal=Journal of neuropathology and experimental neurology|volume=71|issue=9|pages=789–794|doi=10.1097/NEN.0b013e3182656ef8|issn=0022-3069|pmc=3429698|pmid=22892521}}</ref>PMCID:3429698; <ref>{{Cite journal|last=Jones|first=David T. W.|last2=Hutter|first2=Barbara|last3=Jäger|first3=Natalie|last4=Korshunov|first4=Andrey|last5=Kool|first5=Marcel|last6=Warnatz|first6=Hans-Jörg|last7=Zichner|first7=Thomas|last8=Lambert|first8=Sally R.|last9=Ryzhova|first9=Marina|date=2013-08|title=Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma|url=https://pubmed.ncbi.nlm.nih.gov/23817572|journal=Nature Genetics|volume=45|issue=8|pages=927–932|doi=10.1038/ng.2682|issn=1546-1718|pmc=3951336|pmid=23817572}}</ref>PMID:23817572; <ref name=":3">{{Cite journal|last=Zhang|first=Jinghui|last2=Wu|first2=Gang|last3=Miller|first3=Claudia P.|last4=Tatevossian|first4=Ruth G.|last5=Dalton|first5=James D.|last6=Tang|first6=Bo|last7=Orisme|first7=Wilda|last8=Punchihewa|first8=Chandanamali|last9=Parker|first9=Matthew|date=2013-06|title=Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas|url=https://pubmed.ncbi.nlm.nih.gov/23583981|journal=Nature Genetics|volume=45|issue=6|pages=602–612|doi=10.1038/ng.2611|issn=1546-1718|pmc=3727232|pmid=23583981}}</ref>PMID:23583981 <ref>{{Cite journal|last=Jones|first=David T. W.|last2=Kocialkowski|first2=Sylvia|last3=Liu|first3=Lu|last4=Pearson|first4=Danita M.|last5=Bäcklund|first5=L. Magnus|last6=Ichimura|first6=Koichi|last7=Collins|first7=V. Peter|date=2008-11-01|title=Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas|url=https://pubmed.ncbi.nlm.nih.gov/18974108|journal=Cancer Research|volume=68|issue=21|pages=8673–8677|doi=10.1158/0008-5472.CAN-08-2097|issn=1538-7445|pmc=2577184|pmid=18974108}}</ref>PMID:18974108; <ref>{{Cite journal|last=Colin|first=C.|last2=Padovani|first2=L.|last3=Chappé|first3=C.|last4=Mercurio|first4=S.|last5=Scavarda|first5=D.|last6=Loundou|first6=A.|last7=Frassineti|first7=F.|last8=André|first8=N.|last9=Bouvier|first9=C.|date=2013-10|title=Outcome analysis of childhood pilocytic astrocytomas: a retrospective study of 148 cases at a single institution|url=https://pubmed.ncbi.nlm.nih.gov/23278243|journal=Neuropathology and Applied Neurobiology|volume=39|issue=6|pages=693–705|doi=10.1111/nan.12013|issn=1365-2990|pmid=23278243}}</ref>PMID:23278243; <ref name=":4">{{Cite journal|last=Schindler|first=Genevieve|last2=Capper|first2=David|last3=Meyer|first3=Jochen|last4=Janzarik|first4=Wibke|last5=Omran|first5=Heymut|last6=Herold-Mende|first6=Christel|last7=Schmieder|first7=Kirsten|last8=Wesseling|first8=Pieter|last9=Mawrin|first9=Christian|date=2011-03|title=Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma|url=https://pubmed.ncbi.nlm.nih.gov/21274720|journal=Acta Neuropathologica|volume=121|issue=3|pages=397–405|doi=10.1007/s00401-011-0802-6|issn=1432-0533|pmid=21274720}}</ref>PMID:21274720 |
|- | |- | ||
| − | | | + | | |
| − | | Angiocentric glioma | + | |Angiocentric glioma |
| − | | Aberrations involving 6q24-q25 | + | |Aberrations involving 6q24-q25 |
| − | | '''Fusions:''' MYB-QKI rearrangement/deletion (classic histology)<br> | + | |'''Fusions:''' [[MYB]]-[[QKI]] rearrangement/deletion (classic histology)<br> |
| − | '''Rearrangement:''' MYB alone (atypical histology)<br> | + | '''Rearrangement:''' [[MYB]] alone (atypical histology)<br> |
| − | '''Amplification:''' MYB (atypical histology) | + | '''Amplification:''' [[MYB]] (atypical histology) |
| − | | Generally indolent tumors; surgical resection can be curative | + | |Generally indolent tumors; surgical resection can be curative |
| − | | PMID:26829751; PMID:23633565; PMID:26778052 PMID:23583981 | + | |<ref name=":5">{{Cite journal|last=Bandopadhayay|first=Pratiti|last2=Ramkissoon|first2=Lori A.|last3=Jain|first3=Payal|last4=Bergthold|first4=Guillaume|last5=Wala|first5=Jeremiah|last6=Zeid|first6=Rhamy|last7=Schumacher|first7=Steven E.|last8=Urbanski|first8=Laura|last9=O'Rourke|first9=Ryan|date=2016-03|title=MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism|url=https://pubmed.ncbi.nlm.nih.gov/26829751|journal=Nature Genetics|volume=48|issue=3|pages=273–282|doi=10.1038/ng.3500|issn=1546-1718|pmc=4767685|pmid=26829751}}</ref>PMID:26829751; <ref name=":6">{{Cite journal|last=Ramkissoon|first=Lori A.|last2=Horowitz|first2=Peleg M.|last3=Craig|first3=Justin M.|last4=Ramkissoon|first4=Shakti H.|last5=Rich|first5=Benjamin E.|last6=Schumacher|first6=Steven E.|last7=McKenna|first7=Aaron|last8=Lawrence|first8=Michael S.|last9=Bergthold|first9=Guillaume|date=2013-05-14|title=Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1|url=https://pubmed.ncbi.nlm.nih.gov/23633565|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=110|issue=20|pages=8188–8193|doi=10.1073/pnas.1300252110|issn=1091-6490|pmc=3657784|pmid=23633565}}</ref>PMID:23633565; <ref>{{Cite journal|last=Ampie|first=Leonel|last2=Choy|first2=Winward|last3=DiDomenico|first3=Joseph D.|last4=Lamano|first4=Jonathan B.|last5=Williams|first5=Christopher Kazu|last6=Kesavabhotla|first6=Kartik|last7=Mao|first7=Qinwen|last8=Bloch|first8=Orin|date=2016-06|title=Clinical attributes and surgical outcomes of angiocentric gliomas|url=https://pubmed.ncbi.nlm.nih.gov/26778052|journal=Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia|volume=28|pages=117–122|doi=10.1016/j.jocn.2015.11.015|issn=1532-2653|pmid=26778052}}</ref>PMID:26778052 <ref name=":3" />PMID:23583981 |
|- | |- | ||
| | | | ||
| − | | Ganglioglioma | + | |Ganglioglioma |
| − | | Only 30% are abnormal by karyotype '''Gain:''' polysomy 7 | + | |Only 30% are abnormal by karyotype <br> |
| − | | '''Mutations:''' BRAF V600E in 20-60% of cases (can be concurrent with CDKN2A homozygous deletion)<br> | + | '''Gain:''' polysomy 7 |
| − | '''Fusions:''' KIAA1549-BRAF | + | |'''Mutations:''' [[BRAF]] V600E in 20-60% of cases (can be concurrent with [[CDKN2A]] homozygous deletion)<br> |
| − | | Generally indolent tumors for which surgical resection can be curative | + | '''Fusions:''' [[KIAA1549]]-[[BRAF]] |
| − | | PMID:25461780; PMID:23583981; PMID:11996800 PMID:23609006; PMID:29880043 | + | |Generally indolent tumors for which surgical resection can be curative |
| + | |<ref name=":0" />PMID:25461780; <ref name=":3" />PMID:23583981; <ref>{{Cite journal|last=Yin|first=Xiao Lu|last2=Hui|first2=Angela Bik-Yu|last3=Pang|first3=Jesse Chung-Sean|last4=Poon|first4=Wai Sang|last5=Ng|first5=Ho Keung|date=2002-04-01|title=Genome-wide survey for chromosomal imbalances in ganglioglioma using comparative genomic hybridization|url=https://pubmed.ncbi.nlm.nih.gov/11996800|journal=Cancer Genetics and Cytogenetics|volume=134|issue=1|pages=71–76|doi=10.1016/s0165-4608(01)00611-2|issn=0165-4608|pmid=11996800}}</ref>PMID:11996800 <ref>{{Cite journal|last=Dahiya|first=Sonika|last2=Haydon|first2=Devon H.|last3=Alvarado|first3=David|last4=Gurnett|first4=Christina A.|last5=Gutmann|first5=David H.|last6=Leonard|first6=Jeffrey R.|date=2013-06|title=BRAF(V600E) mutation is a negative prognosticator in pediatric ganglioglioma|url=https://pubmed.ncbi.nlm.nih.gov/23609006|journal=Acta Neuropathologica|volume=125|issue=6|pages=901–910|doi=10.1007/s00401-013-1120-y|issn=1432-0533|pmid=23609006}}</ref>PMID:23609006; <ref name=":7">{{Cite journal|last=Pekmezci|first=Melike|last2=Villanueva-Meyer|first2=Javier E.|last3=Goode|first3=Benjamin|last4=Van Ziffle|first4=Jessica|last5=Onodera|first5=Courtney|last6=Grenert|first6=James P.|last7=Bastian|first7=Boris C.|last8=Chamyan|first8=Gabriel|last9=Maher|first9=Ossama M.|date=2018-06-07|title=The genetic landscape of ganglioglioma|url=https://pubmed.ncbi.nlm.nih.gov/29880043|journal=Acta Neuropathologica Communications|volume=6|issue=1|pages=47|doi=10.1186/s40478-018-0551-z|issn=2051-5960|pmc=5992851|pmid=29880043}}</ref>PMID:29880043 | ||
|- | |- | ||
|Low grade glioma, WHO grade II | |Low grade glioma, WHO grade II | ||
|Diffuse astrocytoma | |Diffuse astrocytoma | ||
| − | |No diagnostic aberrations | + | |No diagnostic aberrations |
| − | | '''Rearrangement:''' MYBL1 truncating rearrangements and tandem duplication, FGFR1 rearrangements<br> | + | |'''Rearrangement:''' [[MYBL1]] truncating rearrangements and tandem duplication, [[FGFR1]] rearrangements<br> |
| − | '''Mutation:''' FGFR1 | + | '''Mutation:''' [[FGFR1]] |
| − | | Anaplastic features associated with decreased progression free survival | + | |Anaplastic features associated with decreased progression free survival |
| − | | PMID:25664944; PMID:23633565; PMID:26061751 PMID:26824661; PMID:26004297; PMID:25461780 PMID:23583981 | + | |<ref name=":1" />PMID:25664944; <ref name=":6" />PMID:23633565; <ref name=":8">{{Cite journal|last=Cancer Genome Atlas Research Network|last2=Brat|first2=Daniel J.|last3=Verhaak|first3=Roel G. W.|last4=Aldape|first4=Kenneth D.|last5=Yung|first5=W. K. Alfred|last6=Salama|first6=Sofie R.|last7=Cooper|first7=Lee A. D.|last8=Rheinbay|first8=Esther|last9=Miller|first9=C. Ryan|date=2015-06-25|title=Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas|url=https://pubmed.ncbi.nlm.nih.gov/26061751|journal=The New England Journal of Medicine|volume=372|issue=26|pages=2481–2498|doi=10.1056/NEJMoa1402121|issn=1533-4406|pmc=4530011|pmid=26061751}}</ref>PMID:26061751 <ref name=":9">{{Cite journal|last=Ceccarelli|first=Michele|last2=Barthel|first2=Floris P.|last3=Malta|first3=Tathiane M.|last4=Sabedot|first4=Thais S.|last5=Salama|first5=Sofie R.|last6=Murray|first6=Bradley A.|last7=Morozova|first7=Olena|last8=Newton|first8=Yulia|last9=Radenbaugh|first9=Amie|date=2016-01-28|title=Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma|url=https://pubmed.ncbi.nlm.nih.gov/26824661|journal=Cell|volume=164|issue=3|pages=550–563|doi=10.1016/j.cell.2015.12.028|issn=1097-4172|pmc=4754110|pmid=26824661}}</ref>PMID:26824661; <ref name=":10">{{Cite journal|last=Appin|first=Christina L.|last2=Brat|first2=Daniel J.|date=2015-11|title=Biomarker-driven diagnosis of diffuse gliomas|url=https://pubmed.ncbi.nlm.nih.gov/26004297|journal=Molecular Aspects of Medicine|volume=45|pages=87–96|doi=10.1016/j.mam.2015.05.002|issn=1872-9452|pmid=26004297}}</ref>PMID:26004297; <ref name=":0" />PMID:25461780 <ref name=":3" />PMID:23583981 |
|- | |- | ||
| | | | ||
| − | | Pleomorphic xanthoastrocytoma (PXA) | + | |Pleomorphic xanthoastrocytoma (PXA) |
| − | | Polysomy 3, polysomy 7 observed | + | |Polysomy 3, polysomy 7 observed<br> |
| − | | '''Mutations:''' BRAF V600E in ~60%; TP53 (5%)<br> | + | '''Loss:''' monosomy 9 / 9p deletion |
| − | '''Loss:''' CDKN2A/CDKN2B | + | |'''Mutations:''' [[BRAF]] V600E in ~60%; [[TP53]] (5%)<br> |
| + | '''Loss:''' [[CDKN2A]]/[[CDKN2B]] | ||
| | | | ||
| − | | PMID:25461780; PMID:23583981; PMID:16909113; PMID:12484572 | + | |<ref name=":0" />PMID:25461780; <ref name=":3" />PMID:23583981; <ref>{{Cite journal|last=Weber|first=R. G.|last2=Hoischen|first2=A.|last3=Ehrler|first3=M.|last4=Zipper|first4=P.|last5=Kaulich|first5=K.|last6=Blaschke|first6=B.|last7=Becker|first7=A. J.|last8=Weber-Mangal|first8=S.|last9=Jauch|first9=A.|date=2007-02-15|title=Frequent loss of chromosome 9, homozygous CDKN2A/p14(ARF)/CDKN2B deletion and low TSC1 mRNA expression in pleomorphic xanthoastrocytomas|url=https://pubmed.ncbi.nlm.nih.gov/16909113|journal=Oncogene|volume=26|issue=7|pages=1088–1097|doi=10.1038/sj.onc.1209851|issn=0950-9232|pmid=16909113}}</ref>PMID:16909113; <ref>{{Cite journal|last=Kaulich|first=Kerstin|last2=Blaschke|first2=Britta|last3=Nümann|first3=Astrid|last4=von Deimling|first4=Andreas|last5=Wiestler|first5=Otmar D.|last6=Weber|first6=Ruthild G.|last7=Reifenberger|first7=Guido|date=2002-12|title=Genetic alterations commonly found in diffusely infiltrating cerebral gliomas are rare or absent in pleomorphic xanthoastrocytomas|url=https://pubmed.ncbi.nlm.nih.gov/12484572|journal=Journal of Neuropathology and Experimental Neurology|volume=61|issue=12|pages=1092–1099|doi=10.1093/jnen/61.12.1092|issn=0022-3069|pmid=12484572}}</ref>PMID:12484572 |
|- | |- | ||
| − | | Anaplastic astrocytoma, WHO grade III | + | |Anaplastic astrocytoma, WHO grade III |
| − | | IDH-mutant or IDH-wild type | + | |IDH-mutant or IDH-wild type |
| − | | '''Gain:''' 1q, 7/7q, 8q, 10p<br> | + | |'''Gain:''' 1q, 7/7q, 8q, 10p<br> |
'''Loss:''' 6q, 9p, 10q, -11/11p, 12q, 13q, 14q, 17p, 19q, -22/22q | '''Loss:''' 6q, 9p, 10q, -11/11p, 12q, 13q, 14q, 17p, 19q, -22/22q | ||
| | | | ||
| − | | IDH-wild type astrocytomas can be more clinically aggressive than those that are IDH-mutant | + | |IDH-wild type astrocytomas can be more clinically aggressive than those that are IDH-mutant |
| − | | PMCID:1891902; PMID:26004297; PMID:25461780; PMID:24140581; PMCID:5323185; PMID:27230974 PMID:27196377; PMID:26061751; PMID:25962792; PMID:29687258 | + | |<ref name=":11">{{Cite journal|last=Rickert|first=Christian H.|last2=Sträter|first2=Ronald|last3=Kaatsch|first3=Peter|last4=Wassmann|first4=Hansdetlef|last5=Jürgens|first5=Heribert|last6=Dockhorn-Dworniczak|first6=Barbara|last7=Paulus|first7=Werner|date=2001-4|title=Pediatric High-Grade Astrocytomas Show Chromosomal Imbalances Distinct from Adult Cases|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1891902/|journal=The American Journal of Pathology|volume=158|issue=4|pages=1525–1532|doi=10.1016/S0002-9440(10)64103-X|issn=0002-9440|pmc=1891902|pmid=11290570}}</ref>PMCID:1891902; <ref name=":10" />PMID:26004297; <ref name=":0" />PMID:25461780; <ref>{{Cite journal|last=Killela|first=Patrick J.|last2=Pirozzi|first2=Christopher J.|last3=Reitman|first3=Zachary J.|last4=Jones|first4=Sian|last5=Rasheed|first5=B. Ahmed|last6=Lipp|first6=Eric|last7=Friedman|first7=Henry|last8=Friedman|first8=Allan H.|last9=He|first9=Yiping|date=2014-03-30|title=The genetic landscape of anaplastic astrocytoma|url=https://pubmed.ncbi.nlm.nih.gov/24140581|journal=Oncotarget|volume=5|issue=6|pages=1452–1457|doi=10.18632/oncotarget.1505|issn=1949-2553|pmc=4039223|pmid=24140581}}</ref>PMID:24140581; <ref name=":12">{{Cite journal|last=Koschmann|first=Carl|last2=Zamler|first2=Daniel|last3=MacKay|first3=Alan|last4=Robinson|first4=Dan|last5=Wu|first5=Yi-Mi|last6=Doherty|first6=Robert|last7=Marini|first7=Bernard|last8=Tran|first8=Dustin|last9=Garton|first9=Hugh|date=2016-08-25|title=Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323185/|journal=Oncotarget|volume=7|issue=40|pages=65696–65706|doi=10.18632/oncotarget.11602|issn=1949-2553|pmc=5323185|pmid=27582545}}</ref>PMCID:5323185; <ref>{{Cite journal|last=Grimm|first=Sean A.|last2=Chamberlain|first2=Marc C.|date=2016-07|title=Anaplastic astrocytoma|url=https://pubmed.ncbi.nlm.nih.gov/27230974|journal=CNS oncology|volume=5|issue=3|pages=145–157|doi=10.2217/cns-2016-0002|issn=2045-0915|pmc=6042632|pmid=27230974}}</ref>PMID:27230974 <ref>{{Cite journal|last=Hattori|first=Natsuki|last2=Hirose|first2=Yuichi|last3=Sasaki|first3=Hikaru|last4=Nakae|first4=Shunsuke|last5=Hayashi|first5=Saeko|last6=Ohba|first6=Shigeo|last7=Adachi|first7=Kazuhide|last8=Hayashi|first8=Takuro|last9=Nishiyama|first9=Yuya|date=2016-08|title=World Health Organization grade II-III astrocytomas consist of genetically distinct tumor lineages|url=https://pubmed.ncbi.nlm.nih.gov/27196377|journal=Cancer Science|volume=107|issue=8|pages=1159–1164|doi=10.1111/cas.12969|issn=1349-7006|pmc=4982592|pmid=27196377}}</ref>PMID:27196377; <ref name=":8" />PMID:26061751; <ref>{{Cite journal|last=Reuss|first=David E.|last2=Mamatjan|first2=Yasin|last3=Schrimpf|first3=Daniel|last4=Capper|first4=David|last5=Hovestadt|first5=Volker|last6=Kratz|first6=Annekathrin|last7=Sahm|first7=Felix|last8=Koelsche|first8=Christian|last9=Korshunov|first9=Andrey|date=2015-06|title=IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO|url=https://pubmed.ncbi.nlm.nih.gov/25962792|journal=Acta Neuropathologica|volume=129|issue=6|pages=867–873|doi=10.1007/s00401-015-1438-8|issn=1432-0533|pmc=4500039|pmid=25962792}}</ref>PMID:25962792; <ref name=":13">{{Cite journal|last=Shirahata|first=Mitsuaki|last2=Ono|first2=Takahiro|last3=Stichel|first3=Damian|last4=Schrimpf|first4=Daniel|last5=Reuss|first5=David E.|last6=Sahm|first6=Felix|last7=Koelsche|first7=Christian|last8=Wefers|first8=Annika|last9=Reinhardt|first9=Annekathrin|date=2018-07|title=Novel, improved grading system(s) for IDH-mutant astrocytic gliomas|url=https://pubmed.ncbi.nlm.nih.gov/29687258|journal=Acta Neuropathologica|volume=136|issue=1|pages=153–166|doi=10.1007/s00401-018-1849-4|issn=1432-0533|pmid=29687258}}</ref>PMID:29687258 |
|- | |- | ||
| − | | Other | + | |Other |
| − | | Anaplastic PXA, WHO grade III / Ganglioglioma, WHO Grade III | + | |Anaplastic PXA, WHO grade III / Ganglioglioma, WHO Grade III |
| − | | '''Loss:''' monosomy 9 / 9p deletion, but no diagnostic findings | + | |'''Loss:''' monosomy 9 / 9p deletion, but no diagnostic findings |
| − | | '''Mutation:''' BRAF V600E less common here than in PXA, grade II | + | |'''Mutation:''' [[BRAF]] V600E less common here than in PXA, grade II<br> |
| − | '''Loss:''' CDKN2A/CDKN2B | + | '''Loss:''' [[CDKN2A]]/[[CDKN2B]] |
| − | | CDKN2A/CDKN2B loss may correlate with anaplastic histology | + | |CDKN2A/CDKN2B loss may correlate with anaplastic histology |
| − | | WHO CNS Tumors (2016)<br> | + | |WHO CNS Tumors (2016)<br> |
| − | PMID:25318587; PMID:23096133; PMID:21274720 | + | <ref>{{Cite journal|last=Ida|first=Cristiane M.|last2=Rodriguez|first2=Fausto J.|last3=Burger|first3=Peter C.|last4=Caron|first4=Alissa A.|last5=Jenkins|first5=Sarah M.|last6=Spears|first6=Grant M.|last7=Aranguren|first7=Dawn L.|last8=Lachance|first8=Daniel H.|last9=Giannini|first9=Caterina|date=2015-09|title=Pleomorphic Xanthoastrocytoma: Natural History and Long-Term Follow-Up|url=https://pubmed.ncbi.nlm.nih.gov/25318587|journal=Brain Pathology (Zurich, Switzerland)|volume=25|issue=5|pages=575–586|doi=10.1111/bpa.12217|issn=1750-3639|pmc=4400218|pmid=25318587}}</ref>PMID:25318587; <ref>{{Cite journal|last=Schmidt|first=Yao|last2=Kleinschmidt-DeMasters|first2=B. K.|last3=Aisner|first3=Dara L.|last4=Lillehei|first4=Kevin O.|last5=Damek|first5=Denise|date=2013-01|title=Anaplastic PXA in adults: case series with clinicopathologic and molecular features|url=https://pubmed.ncbi.nlm.nih.gov/23096133|journal=Journal of Neuro-Oncology|volume=111|issue=1|pages=59–69|doi=10.1007/s11060-012-0991-4|issn=1573-7373|pmc=4617340|pmid=23096133}}</ref>PMID:23096133; <ref name=":4" />PMID:21274720 |
|- | |- | ||
|Glioblastoma, WHO grade IV | |Glioblastoma, WHO grade IV | ||
| − | |IDH-mutant | + | |IDH-mutant |
| − | |'''Gain:''' 1q, 2q, 3q, 7, 16p, 17q, 21q | + | |'''Gain:''' 1q, 2q, 3q, 7, 16p, 17q, 21q<br> |
| − | '''Loss:''' 6q, 8q, 9p, 9q, 10q, 13q, 17p, 22q | + | '''Loss:''' 6q, 8q, 9p, 9q, 10q, 13q, 17p, 22q<br> |
''' Chromothripsis:''' observed | ''' Chromothripsis:''' observed | ||
| − | |'''Loss:''' PTEN, RB1, TP53, CDKN2A/ | + | |'''Loss:''' [[PTEN]], [[RB1]], [[TP53]], [[CDKN2A]]/[[CDKN2B]]/[[CDKN2C]] |
| − | '''Fusions:''' FGFR-TACC; NTRK fusions | + | '''Fusions:''' FGFR-[[TACC]]; NTRK fusions <br> |
| − | '''Amplification:''' PDGFRA, MYCN, MET, CDK4, CDK6 (EGFR, MDM2 amp rare)<br> | + | '''Amplification:''' [[PDGFRA]], [[MYCN]], [[MET]], [[CDK4]], [[CDK6]] ([[EGFR]], [[MDM2]] amp rare)<br> |
| − | '''Mutations:''' IDH1/ | + | '''Mutations:''' [[IDH1]]/[[IDH2]] (rare in pediatric GBM), [[KRAS]], RAS pathway, [[RB1]] pathway, [[TP53]] pathway, [[FGFR1]], H3.3/H3.1-K27M (exclusively in diffuse midline tumors), [[PDGFRA]], [[NF1]], [[SETD2]], [[ATRX]], [[DAXX]] |
| − | | Overall poor prognosis | + | |Overall poor prognosis |
| − | |PMID:25752754; PMID:25727226; PMID:26328271; PMID:22837387; PMID:25754088; PMID:25461780; PMCID:1891902; PMID:23417712; PMCID:5323185; | + | |<ref>{{Cite journal|last=Korshunov|first=Andrey|last2=Ryzhova|first2=Marina|last3=Hovestadt|first3=Volker|last4=Bender|first4=Sebastian|last5=Sturm|first5=Dominik|last6=Capper|first6=David|last7=Meyer|first7=Jochen|last8=Schrimpf|first8=Daniel|last9=Kool|first9=Marcel|date=2015-05|title=Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers|url=https://pubmed.ncbi.nlm.nih.gov/25752754|journal=Acta Neuropathologica|volume=129|issue=5|pages=669–678|doi=10.1007/s00401-015-1405-4|issn=1432-0533|pmid=25752754}}</ref>PMID:25752754; <ref name=":14">{{Cite journal|last=Karsy|first=Michael|last2=Neil|first2=Jayson A.|last3=Guan|first3=Jian|last4=Mahan|first4=Mark A.|last5=Mark|first5=Mahan A.|last6=Colman|first6=Howard|last7=Jensen|first7=Randy L.|date=2015-03|title=A practical review of prognostic correlations of molecular biomarkers in glioblastoma|url=https://pubmed.ncbi.nlm.nih.gov/25727226|journal=Neurosurgical Focus|volume=38|issue=3|pages=E4|doi=10.3171/2015.1.FOCUS14755|issn=1092-0684|pmid=25727226}}</ref>PMID:25727226; <ref>{{Cite journal|last=Furgason|first=John M.|last2=Koncar|first2=Robert F.|last3=Michelhaugh|first3=Sharon K.|last4=Sarkar|first4=Fazlul H.|last5=Mittal|first5=Sandeep|last6=Sloan|first6=Andrew E.|last7=Barnholtz-Sloan|first7=Jill S.|last8=Bahassi|first8=El Mustapha|date=2015|title=Whole genome sequence analysis links chromothripsis to EGFR, MDM2, MDM4, and CDK4 amplification in glioblastoma|url=https://pubmed.ncbi.nlm.nih.gov/26328271|journal=Oncoscience|volume=2|issue=7|pages=618–628|doi=10.18632/oncoscience.178|issn=2331-4737|pmc=4549359|pmid=26328271}}</ref>PMID:26328271; <ref>{{Cite journal|last=Singh|first=Devendra|last2=Chan|first2=Joseph Minhow|last3=Zoppoli|first3=Pietro|last4=Niola|first4=Francesco|last5=Sullivan|first5=Ryan|last6=Castano|first6=Angelica|last7=Liu|first7=Eric Minwei|last8=Reichel|first8=Jonathan|last9=Porrati|first9=Paola|date=2012-09-07|title=Transforming fusions of FGFR and TACC genes in human glioblastoma|url=https://pubmed.ncbi.nlm.nih.gov/22837387|journal=Science (New York, N.Y.)|volume=337|issue=6099|pages=1231–1235|doi=10.1126/science.1220834|issn=1095-9203|pmc=3677224|pmid=22837387}}</ref>PMID:22837387; <ref name=":15">{{Cite journal|last=Ramkissoon|first=Shakti H.|last2=Bi|first2=Wenya Linda|last3=Schumacher|first3=Steven E.|last4=Ramkissoon|first4=Lori A.|last5=Haidar|first5=Sam|last6=Knoff|first6=David|last7=Dubuc|first7=Adrian|last8=Brown|first8=Loreal|last9=Burns|first9=Margot|date=2015-10|title=Clinical implementation of integrated whole-genome copy number and mutation profiling for glioblastoma|url=https://pubmed.ncbi.nlm.nih.gov/25754088|journal=Neuro-Oncology|volume=17|issue=10|pages=1344–1355|doi=10.1093/neuonc/nov015|issn=1523-5866|pmc=4578577|pmid=25754088}}</ref>PMID:25754088; <ref name=":0" />PMID:25461780; <ref name=":11" />PMCID:1891902; <ref>{{Cite journal|last=Fontebasso|first=Adam M.|last2=Schwartzentruber|first2=Jeremy|last3=Khuong-Quang|first3=Dong-Anh|last4=Liu|first4=Xiao-Yang|last5=Sturm|first5=Dominik|last6=Korshunov|first6=Andrey|last7=Jones|first7=David T. W.|last8=Witt|first8=Hendrik|last9=Kool|first9=Marcel|date=2013-05|title=Mutations in SETD2 and genes affecting histone H3K36 methylation target hemispheric high-grade gliomas|url=https://pubmed.ncbi.nlm.nih.gov/23417712|journal=Acta Neuropathologica|volume=125|issue=5|pages=659–669|doi=10.1007/s00401-013-1095-8|issn=1432-0533|pmc=3631313|pmid=23417712}}</ref>PMID:23417712; <ref name=":12" />PMCID:5323185; <ref name=":13" />PMID:29687258; <ref>{{Cite journal|last=Paugh|first=Barbara S.|last2=Qu|first2=Chunxu|last3=Jones|first3=Chris|last4=Liu|first4=Zhaoli|last5=Adamowicz-Brice|first5=Martyna|last6=Zhang|first6=Junyuan|last7=Bax|first7=Dorine A.|last8=Coyle|first8=Beth|last9=Barrow|first9=Jennifer|date=2010-06-20|title=Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease|url=https://pubmed.ncbi.nlm.nih.gov/20479398|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=28|issue=18|pages=3061–3068|doi=10.1200/JCO.2009.26.7252|issn=1527-7755|pmc=2903336|pmid=20479398}}</ref>PMID:20479398; <ref>{{Cite journal|last=Giunti|first=Laura|last2=Pantaleo|first2=Marilena|last3=Sardi|first3=Iacopo|last4=Provenzano|first4=Aldesia|last5=Magi|first5=Alberto|last6=Cardellicchio|first6=Stefania|last7=Castiglione|first7=Francesca|last8=Tattini|first8=Lorenzo|last9=Novara|first9=Francesca|date=2014|title=Genome-wide copy number analysis in pediatric glioblastoma multiforme|url=https://pubmed.ncbi.nlm.nih.gov/24959384|journal=American Journal of Cancer Research|volume=4|issue=3|pages=293–303|issn=2156-6976|pmc=4065410|pmid=24959384}}</ref>PMID:24959384 |
|- | |- | ||
|Diffuse midline glioma, H3 K27M mutant | |Diffuse midline glioma, H3 K27M mutant | ||
| Line 95: | Line 97: | ||
'''Chromothripsis:''' 2p | '''Chromothripsis:''' 2p | ||
|'''Three molecular subgroups:''' <br> | |'''Three molecular subgroups:''' <br> | ||
| − | '''MYCN subgroup:''' no mutations but chromothripsis leading to amp of MYCN and ID2<br> | + | '''MYCN subgroup:''' no mutations but chromothripsis leading to amp of [[MYCN]] and [[ID2]]<br> |
'''Silent subgroup:''' no recurrent copy # changes, few mutations<br> | '''Silent subgroup:''' no recurrent copy # changes, few mutations<br> | ||
| − | '''H3-K27M subgroup:''' MYC, PDGFRA gains/amp; RB1, TP53 deletions<br> | + | '''H3-K27M subgroup:''' [[MYC]], [[PDGFRA]] gains/amp; [[RB1]], [[TP53]] deletions<br> |
| − | '''Mutation:''' ACVR1, H3F3A, HIST1H3B, TP53 '''Loss:''' CDKN2A, PTEN, RB1, TP53<br> | + | '''Mutation:''' [[ACVR1]], [[H3F3A]], [[HIST1H3B]], [[TP53]] '''Loss:''' [[CDKN2A]], [[PTEN]], [[RB1]], [[TP53]]<br> |
| − | '''Amplification:''' MYC, MYCN, ID2, PDGFRA | + | '''Amplification:''' [[MYC]], [[MYCN]], [[ID2]], [[PDGFRA]] |
|Overall poor prognosis regardless of subgroup | |Overall poor prognosis regardless of subgroup | ||
| − | |PMCID:3280796; PMID:24705254; PMID:24705252 PMID:27048880; PMID:26175967; PMID:24705251; PMID:28966033 | + | |<ref>{{Cite journal|last=Warren|first=Katherine E.|last2=Killian|first2=Keith|last3=Suuriniemi|first3=Miia|last4=Wang|first4=Yonghong|last5=Quezado|first5=Martha|last6=Meltzer|first6=Paul S.|date=2012-3|title=Genomic aberrations in pediatric diffuse intrinsic pontine gliomas|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280796/|journal=Neuro-Oncology|volume=14|issue=3|pages=326–332|doi=10.1093/neuonc/nor190|issn=1522-8517|pmc=3280796|pmid=22064882}}</ref>PMCID:3280796; <ref>{{Cite journal|last=Buczkowicz|first=Pawel|last2=Hoeman|first2=Christine|last3=Rakopoulos|first3=Patricia|last4=Pajovic|first4=Sanja|last5=Letourneau|first5=Louis|last6=Dzamba|first6=Misko|last7=Morrison|first7=Andrew|last8=Lewis|first8=Peter|last9=Bouffet|first9=Eric|date=2014-05|title=Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations|url=https://pubmed.ncbi.nlm.nih.gov/24705254|journal=Nature Genetics|volume=46|issue=5|pages=451–456|doi=10.1038/ng.2936|issn=1546-1718|pmc=3997489|pmid=24705254}}</ref>PMID:24705254; <ref>{{Cite journal|last=Taylor|first=Kathryn R.|last2=Mackay|first2=Alan|last3=Truffaux|first3=Nathalène|last4=Butterfield|first4=Yaron|last5=Morozova|first5=Olena|last6=Philippe|first6=Cathy|last7=Castel|first7=David|last8=Grasso|first8=Catherine S.|last9=Vinci|first9=Maria|date=2014-05|title=Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma|url=https://pubmed.ncbi.nlm.nih.gov/24705252|journal=Nature Genetics|volume=46|issue=5|pages=457–461|doi=10.1038/ng.2925|issn=1546-1718|pmc=4018681|pmid=24705252}}</ref>PMID:24705252 <ref>{{Cite journal|last=Nikbakht|first=Hamid|last2=Panditharatna|first2=Eshini|last3=Mikael|first3=Leonie G.|last4=Li|first4=Rui|last5=Gayden|first5=Tenzin|last6=Osmond|first6=Matthew|last7=Ho|first7=Cheng-Ying|last8=Kambhampati|first8=Madhuri|last9=Hwang|first9=Eugene I.|date=2016-04-06|title=Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma|url=https://pubmed.ncbi.nlm.nih.gov/27048880|journal=Nature Communications|volume=7|pages=11185|doi=10.1038/ncomms11185|issn=2041-1723|pmc=4823825|pmid=27048880}}</ref>PMID:27048880; <ref>{{Cite journal|last=Buczkowicz|first=Pawel|last2=Hawkins|first2=Cynthia|date=2015|title=Pathology, Molecular Genetics, and Epigenetics of Diffuse Intrinsic Pontine Glioma|url=https://pubmed.ncbi.nlm.nih.gov/26175967|journal=Frontiers in Oncology|volume=5|pages=147|doi=10.3389/fonc.2015.00147|issn=2234-943X|pmc=4485076|pmid=26175967}}</ref>PMID:26175967; <ref>{{Cite journal|last=Wu|first=Gang|last2=Diaz|first2=Alexander K.|last3=Paugh|first3=Barbara S.|last4=Rankin|first4=Sherri L.|last5=Ju|first5=Bensheng|last6=Li|first6=Yongjin|last7=Zhu|first7=Xiaoyan|last8=Qu|first8=Chunxu|last9=Chen|first9=Xiang|date=2014-05|title=The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma|url=https://pubmed.ncbi.nlm.nih.gov/24705251|journal=Nature Genetics|volume=46|issue=5|pages=444–450|doi=10.1038/ng.2938|issn=1546-1718|pmc=4056452|pmid=24705251}}</ref>PMID:24705251; <ref>{{Cite journal|last=Mackay|first=Alan|last2=Burford|first2=Anna|last3=Carvalho|first3=Diana|last4=Izquierdo|first4=Elisa|last5=Fazal-Salom|first5=Janat|last6=Taylor|first6=Kathryn R.|last7=Bjerke|first7=Lynn|last8=Clarke|first8=Matthew|last9=Vinci|first9=Mara|date=2017-10-09|title=Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma|url=https://pubmed.ncbi.nlm.nih.gov/28966033|journal=Cancer Cell|volume=32|issue=4|pages=520–537.e5|doi=10.1016/j.ccell.2017.08.017|issn=1878-3686|pmc=5637314|pmid=28966033}}</ref>PMID:28966033 |
|- | |- | ||
|'''EPENDYMOMA'''<br> | |'''EPENDYMOMA'''<br> | ||
| Line 107: | Line 109: | ||
| | | | ||
|'''DNA-based methylation classifies''' tumors across anatomical sites (posterior fossa, supratentorial, spinal), grades and age groups | |'''DNA-based methylation classifies''' tumors across anatomical sites (posterior fossa, supratentorial, spinal), grades and age groups | ||
| − | |'''Fusion:''' YAP1 fusions (supratentorial tumors)<br> | + | |'''Fusion:''' [[YAP1]] fusions (supratentorial tumors)<br> |
| − | '''Mutation:''' NF2 (spinal tumors)<br> | + | '''Mutation:''' [[NF2]] (spinal tumors)<br> |
| − | '''Loss:''' CDKN2A | + | '''Loss:''' [[CDKN2A]] |
|Intracranial (in children, 90%) or spinal tumors; Histological distinction between WHO grade II and III is of questionable relevance; Prognostic differences among tumors suggested on the basis of methylation analysis | |Intracranial (in children, 90%) or spinal tumors; Histological distinction between WHO grade II and III is of questionable relevance; Prognostic differences among tumors suggested on the basis of methylation analysis | ||
|WHO CNS Tumors (2016)<br> | |WHO CNS Tumors (2016)<br> | ||
| − | PMID:25965575; PMID:21627842; PMID:24939246; PMID:22516549 | + | <ref name=":16">{{Cite journal|last=Pajtler|first=Kristian W.|last2=Witt|first2=Hendrik|last3=Sill|first3=Martin|last4=Jones|first4=David T. W.|last5=Hovestadt|first5=Volker|last6=Kratochwil|first6=Fabian|last7=Wani|first7=Khalida|last8=Tatevossian|first8=Ruth|last9=Punchihewa|first9=Chandanamali|date=2015-05-11|title=Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups|url=https://pubmed.ncbi.nlm.nih.gov/25965575|journal=Cancer Cell|volume=27|issue=5|pages=728–743|doi=10.1016/j.ccell.2015.04.002|issn=1878-3686|pmc=4712639|pmid=25965575}}</ref>PMID:25965575; <ref name=":17">{{Cite journal|last=Ellison|first=David W.|last2=Kocak|first2=Mehmet|last3=Figarella-Branger|first3=Dominique|last4=Felice|first4=Giangaspero|last5=Catherine|first5=Godfraind|last6=Pietsch|first6=Torsten|last7=Frappaz|first7=Didier|last8=Massimino|first8=Maura|last9=Grill|first9=Jacques|date=2011-05-31|title=Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts|url=https://pubmed.ncbi.nlm.nih.gov/21627842|journal=Journal of Negative Results in Biomedicine|volume=10|pages=7|doi=10.1186/1477-5751-10-7|issn=1477-5751|pmc=3117833|pmid=21627842}}</ref>PMID:21627842; <ref name=":18">{{Cite journal|last=Olsen|first=Thale Kristin|last2=Gorunova|first2=Ludmila|last3=Meling|first3=Torstein R.|last4=Micci|first4=Francesca|last5=Scheie|first5=David|last6=Due-Tønnessen|first6=Bernt|last7=Heim|first7=Sverre|last8=Brandal|first8=Petter|date=2014-08|title=Genomic characterization of ependymomas reveals 6q loss as the most common aberration|url=https://pubmed.ncbi.nlm.nih.gov/24939246|journal=Oncology Reports|volume=32|issue=2|pages=483–490|doi=10.3892/or.2014.3271|issn=1791-2431|pmc=4091878|pmid=24939246}}</ref>PMID:24939246; <ref name=":19">{{Cite journal|last=Yang|first=Isaac|last2=Nagasawa|first2=Daniel T.|last3=Kim|first3=Won|last4=Spasic|first4=Marko|last5=Trang|first5=Andy|last6=Lu|first6=Daniel C.|last7=Martin|first7=Neil A.|date=2012-06|title=Chromosomal anomalies and prognostic markers for intracranial and spinal ependymomas|url=https://pubmed.ncbi.nlm.nih.gov/22516549|journal=Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia|volume=19|issue=6|pages=779–785|doi=10.1016/j.jocn.2011.11.004|issn=1532-2653|pmc=3615711|pmid=22516549}}</ref>PMID:22516549 |
|- | |- | ||
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| Line 119: | Line 121: | ||
'''Loss:''' 1p, 3, -6/6q, 9p, 13q, 17, 22 | '''Loss:''' 1p, 3, -6/6q, 9p, 13q, 17, 22 | ||
|Usually intracranial, spinal tumors (myxopapillary) are rare; 80% of pediatric tumors develop in posterior fossa (PF); Supratentorial tumors preferentially show monosomy 9; 1q gain is unfavorable prognostic indicator in PF tumors; spinal tumors associated with NF2 (germline); children have worse outcomes than adults | |Usually intracranial, spinal tumors (myxopapillary) are rare; 80% of pediatric tumors develop in posterior fossa (PF); Supratentorial tumors preferentially show monosomy 9; 1q gain is unfavorable prognostic indicator in PF tumors; spinal tumors associated with NF2 (germline); children have worse outcomes than adults | ||
| − | |PMID:25965575; PMID:22338015; PMID:28371821 | + | |<ref name=":16" />PMID:25965575; <ref name=":21">{{Cite journal|last=Kilday|first=John-Paul|last2=Mitra|first2=Biswaroop|last3=Domerg|first3=Caroline|last4=Ward|first4=Jennifer|last5=Andreiuolo|first5=Felipe|last6=Osteso-Ibanez|first6=Teresa|last7=Mauguen|first7=Audrey|last8=Varlet|first8=Pascale|last9=Le Deley|first9=Marie-Cecile|date=2012-04-01|title=Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification: a prospective European clinical trial cohort analysis on behalf of the Children's Cancer Leukaemia Group (CCLG), Societe Francaise d'Oncologie Pediatrique (SFOP), and International Society for Pediatric Oncology (SIOP)|url=https://pubmed.ncbi.nlm.nih.gov/22338015|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=18|issue=7|pages=2001–2011|doi=10.1158/1078-0432.CCR-11-2489|issn=1557-3265|pmid=22338015}}</ref>PMID:22338015; <ref name=":22">{{Cite journal|last=Gojo|first=Johannes|last2=Lötsch|first2=Daniela|last3=Spiegl-Kreinecker|first3=Sabine|last4=Pajtler|first4=Kristian W.|last5=Neumayer|first5=Katharina|last6=Korbel|first6=Pia|last7=Araki|first7=Asuka|last8=Brandstetter|first8=Anita|last9=Mohr|first9=Thomas|date=2017-09-01|title=Telomerase activation in posterior fossa group A ependymomas is associated with dismal prognosis and chromosome 1q gain|url=https://pubmed.ncbi.nlm.nih.gov/28371821|journal=Neuro-Oncology|volume=19|issue=9|pages=1183–1194|doi=10.1093/neuonc/nox027|issn=1523-5866|pmc=5570194|pmid=28371821}}</ref>PMID:28371821 |
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| Line 128: | Line 130: | ||
|Favorable prognosis | |Favorable prognosis | ||
|WHO CNS Tumors (2016) <br> | |WHO CNS Tumors (2016) <br> | ||
| − | PMID:21959044; PMID:21840481<br> | + | <ref name=":20">{{Cite journal|last=Yao|first=Yuan|last2=Mack|first2=Stephen C.|last3=Taylor|first3=Michael D.|date=2011-10|title=Molecular genetics of ependymoma|url=https://pubmed.ncbi.nlm.nih.gov/21959044|journal=Chinese Journal of Cancer|volume=30|issue=10|pages=669–681|doi=10.5732/cjc.011.10129|issn=1000-467X|pmc=4012267|pmid=21959044}}</ref>PMID:21959044; <ref name=":23">{{Cite journal|last=Witt|first=Hendrik|last2=Mack|first2=Stephen C.|last3=Ryzhova|first3=Marina|last4=Bender|first4=Sebastian|last5=Sill|first5=Martin|last6=Isserlin|first6=Ruth|last7=Benner|first7=Axel|last8=Hielscher|first8=Thomas|last9=Milde|first9=Till|date=2011-08-16|title=Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma|url=https://pubmed.ncbi.nlm.nih.gov/21840481|journal=Cancer Cell|volume=20|issue=2|pages=143–157|doi=10.1016/j.ccr.2011.07.007|issn=1878-3686|pmc=4154494|pmid=21840481}}</ref>PMID:21840481<br> |
|- | |- | ||
| | | | ||
|Myxopapillary ependymoma, WHO grade I | |Myxopapillary ependymoma, WHO grade I | ||
|'''Aneuploidy:''' multiple chromosomes lost and gained | |'''Aneuploidy:''' multiple chromosomes lost and gained | ||
| − | |'''Mutation:''' NF2 (including germline) in spinal tumors | + | |'''Mutation:''' [[NF2]] (including germline) in spinal tumors |
|Less common but more aggressive in children | |Less common but more aggressive in children | ||
| − | |PMID:25965575; PMCID:3991130; PMID:20425037; PMID:25957288; | + | |<ref name=":16" />PMID:25965575; <ref name=":24">{{Cite journal|last=Zadnik|first=Patricia L.|last2=Gokaslan|first2=Ziya L.|last3=Burger|first3=Peter C.|last4=Bettegowda|first4=Chetan|date=2013-5|title=Spinal cord tumours: advances in genetics and their implications for treatment|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991130/|journal=Nature reviews. Neurology|volume=9|issue=5|pages=257–266|doi=10.1038/nrneurol.2013.48|issn=1759-4758|pmc=3991130|pmid=23528542}}</ref>PMCID:3991130; <ref name=":25">{{Cite journal|last=Dubuc|first=Adrian M.|last2=Northcott|first2=Paul A.|last3=Mack|first3=Stephen|last4=Witt|first4=Hendrik|last5=Pfister|first5=Stefan|last6=Taylor|first6=Michael D.|date=2010-05|title=The genetics of pediatric brain tumors|url=https://pubmed.ncbi.nlm.nih.gov/20425037|journal=Current Neurology and Neuroscience Reports|volume=10|issue=3|pages=215–223|doi=10.1007/s11910-010-0103-9|issn=1534-6293|pmid=20425037}}</ref>PMID:20425037; <ref name=":26">{{Cite journal|last=Mack|first=Stephen C.|last2=Agnihotri|first2=Sameer|last3=Bertrand|first3=Kelsey C.|last4=Wang|first4=Xin|last5=Shih|first5=David J.|last6=Witt|first6=Hendrik|last7=Hill|first7=Nadia|last8=Zayne|first8=Kory|last9=Barszczyk|first9=Mark|date=2015-08-15|title=Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype|url=https://pubmed.ncbi.nlm.nih.gov/25957288|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=21|issue=16|pages=3750–3758|doi=10.1158/1078-0432.CCR-14-2650|issn=1557-3265|pmc=4537825|pmid=25957288}}</ref>PMID:25957288; <ref name=":19" />PMID:22516549 |
|- | |- | ||
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| Line 142: | Line 144: | ||
'''Aneuploidy:''' multiple chromosomes lost and gained<br> | '''Aneuploidy:''' multiple chromosomes lost and gained<br> | ||
'''Chromothripsis:''' chromosome 11 (70% of supratentorial tumors) | '''Chromothripsis:''' chromosome 11 (70% of supratentorial tumors) | ||
| − | |'''Fusion:''' | + | |'''Fusion:''' [[C11ORF95]]-[[RELA]] (supratentorial tumors)<br> |
| − | '''Loss:''' CDKN2A/ | + | '''Loss:''' [[CDKN2A]]/[[CDKN2B]] (may help distinguish from other supratentorial ependymomas) |
|Unfavorable prognosis; occur in infants or children | |Unfavorable prognosis; occur in infants or children | ||
| − | |PMID:25965575; PMID:24553141; PMID:28371821 | + | |<ref name=":16" />PMID:25965575; <ref name=":27">{{Cite journal|last=Parker|first=Matthew|last2=Mohankumar|first2=Kumarasamypet M.|last3=Punchihewa|first3=Chandanamali|last4=Weinlich|first4=Ricardo|last5=Dalton|first5=James D.|last6=Li|first6=Yongjin|last7=Lee|first7=Ryan|last8=Tatevossian|first8=Ruth G.|last9=Phoenix|first9=Timothy N.|date=2014-02-27|title=C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma|url=https://pubmed.ncbi.nlm.nih.gov/24553141|journal=Nature|volume=506|issue=7489|pages=451–455|doi=10.1038/nature13109|issn=1476-4687|pmc=4050669|pmid=24553141}}</ref>PMID:24553141; <ref name=":22" />PMID:28371821 |
|- | |- | ||
| | | | ||
|Anaplastic ependymoma (no WHO grade assigned) | |Anaplastic ependymoma (no WHO grade assigned) | ||
|Epigenetic studies suggest range of abnormalities: balanced or unbalanced genomes | |Epigenetic studies suggest range of abnormalities: balanced or unbalanced genomes | ||
| − | |'''Mutation:''' NF2 (including germline) in spinal tumors<br> | + | |'''Mutation:''' [[NF2]] (including germline) in spinal tumors<br> |
| − | '''Fusion:''' RELA fusions, YAP1 fusions can correspond to anaplastic histology | + | '''Fusion:''' [[RELA]] fusions, [[YAP1]] fusions can correspond to anaplastic histology |
|Mostly intracranial tumors, rarely in spinal cord; YAP1 fusion tumors can occur in infants | |Mostly intracranial tumors, rarely in spinal cord; YAP1 fusion tumors can occur in infants | ||
| − | |PMID: 25965575 | + | |<ref name=":16" />PMID: 25965575 |
|- | |- | ||
|'''EMBRYONAL TUMORS''' | |'''EMBRYONAL TUMORS''' | ||
| Line 163: | Line 165: | ||
|- | |- | ||
|Medulloblastoma | |Medulloblastoma | ||
| − | |WNT-activated | + | |WNT-activated |
| − | |'''Loss:''' monosomy 6/6q- as sole finding in 85% | + | |'''Loss:''' monosomy 6/6q- as sole finding in 85% |
| − | |'''Mutation:''' CTNNB1, DDX3X, TP53, SMARCA4, KMT2D, APC (germline mutations in Turcot syndrome) | + | |'''Mutation:''' [[CTNNB1]], [[DDX3X]], [[TP53]], [[SMARCA4]], [[KMT2D]], [[APC]] (germline mutations in Turcot syndrome) |
|Common in children > 3 years of age; typically show classic histology, rarely metastasize; overall favorable prognosis | |Common in children > 3 years of age; typically show classic histology, rarely metastasize; overall favorable prognosis | ||
| − | |PMID:22832581, PMID:24493713; PMID:22134537 PMID:24894640; PMID:16258095; | + | |<ref name=":28">{{Cite journal|last=Northcott|first=Paul A.|last2=Shih|first2=David J. H.|last3=Peacock|first3=John|last4=Garzia|first4=Livia|last5=Morrissy|first5=A. Sorana|last6=Zichner|first6=Thomas|last7=Stütz|first7=Adrian M.|last8=Korshunov|first8=Andrey|last9=Reimand|first9=Jüri|date=2012-08-02|title=Subgroup-specific structural variation across 1,000 medulloblastoma genomes|url=https://pubmed.ncbi.nlm.nih.gov/22832581|journal=Nature|volume=488|issue=7409|pages=49–56|doi=10.1038/nature11327|issn=1476-4687|pmc=3683624|pmid=22832581}}</ref>PMID:22832581, <ref name=":29">{{Cite journal|last=Shih|first=David J. 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|- | |- | ||
| | | | ||
| − | |SHH-activated | + | |SHH-activated |
|'''Gain:''' 3q<br> | |'''Gain:''' 3q<br> | ||
'''Loss:''' 9q, 10q, 17p<br> | '''Loss:''' 9q, 10q, 17p<br> | ||
| Line 176: | Line 178: | ||
'''Chromothripsis:''' associated with TP53 mutation | '''Chromothripsis:''' associated with TP53 mutation | ||
|'''Mutation:'''<br> | |'''Mutation:'''<br> | ||
| − | '''TP53 wild-type tumors:''' PTCH1 (germline mutations in Gorlin syndrome), SMO, SUFU (can be germline), TERT promoter<br> | + | '''TP53 wild-type tumors:''' [[PTCH1]] (germline mutations in Gorlin syndrome), [[SMO]], [[SUFU]] (can be germline), [[TERT]] promoter<br> |
| − | '''TP53-mutant tumors:''' can be germline<br> | + | '''[[TP53]]-mutant tumors:''' can be germline<br> |
| − | '''Loss:''' PTCH1, PTEN<br> | + | '''Loss:''' [[PTCH1]], [[PTEN]]<br> |
| − | '''Amplification:''' GLI2 (TP53-mutant tumors), IGF1R, PPM1D, MYCN (TP53-mutant tumors), YAP1, MIR17/92, MDM4 | + | '''Amplification:''' [[GLI2]] ([[TP53]]-mutant tumors), [[IGF1R]], [[PPM1D]], [[MYCN]] ([[TP53]]-mutant tumors), [[YAP1]], MIR17/92, [[MDM4]] |
|Common in infants, rare in children, most common type of medulloblastoma in adults; Desmoplastic (or nodular) histology common; TP53 wild-type usually correlate with extensive nodularity or desmoplastic histology; TP53-mutant tumors correlate with metastatic disease | |Common in infants, rare in children, most common type of medulloblastoma in adults; Desmoplastic (or nodular) histology common; TP53 wild-type usually correlate with extensive nodularity or desmoplastic histology; TP53-mutant tumors correlate with metastatic disease | ||
| − | |PMID:24651015; PMID:21681522; PMID:22832581 PMID:24493713; PMID:24077351; PMID:22134537; | + | |<ref>{{Cite journal|last=Kool|first=Marcel|last2=Jones|first2=David T. W.|last3=Jäger|first3=Natalie|last4=Northcott|first4=Paul A.|last5=Pugh|first5=Trevor J.|last6=Hovestadt|first6=Volker|last7=Piro|first7=Rosario M.|last8=Esparza|first8=L. Adriana|last9=Markant|first9=Shirley L.|date=2014-03-17|title=Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition|url=https://pubmed.ncbi.nlm.nih.gov/24651015|journal=Cancer Cell|volume=25|issue=3|pages=393–405|doi=10.1016/j.ccr.2014.02.004|issn=1878-3686|pmc=4493053|pmid=24651015}}</ref>PMID:24651015; <ref>{{Cite journal|last=Northcott|first=Paul A.|last2=Hielscher|first2=Thomas|last3=Dubuc|first3=Adrian|last4=Mack|first4=Stephen|last5=Shih|first5=David|last6=Remke|first6=Marc|last7=Al-Halabi|first7=Hani|last8=Albrecht|first8=Steffen|last9=Jabado|first9=Nada|date=2011-08|title=Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct|url=https://pubmed.ncbi.nlm.nih.gov/21681522|journal=Acta Neuropathologica|volume=122|issue=2|pages=231–240|doi=10.1007/s00401-011-0846-7|issn=1432-0533|pmc=4538327|pmid=21681522}}</ref>PMID:21681522; <ref name=":28" />PMID:22832581 <ref name=":29" />PMID:24493713; <ref>{{Cite journal|last=Gajjar|first=Amar|last2=Stewart|first2=Clinton F.|last3=Ellison|first3=David W.|last4=Kaste|first4=Sue|last5=Kun|first5=Larry E.|last6=Packer|first6=Roger J.|last7=Goldman|first7=Stewart|last8=Chintagumpala|first8=Murali|last9=Wallace|first9=Dana|date=2013-11-15|title=Phase I study of vismodegib in children with recurrent or refractory medulloblastoma: a pediatric brain tumor consortium study|url=https://pubmed.ncbi.nlm.nih.gov/24077351|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=19|issue=22|pages=6305–6312|doi=10.1158/1078-0432.CCR-13-1425|issn=1557-3265|pmc=3856244|pmid=24077351}}</ref>PMID:24077351; <ref name=":30" />PMID:22134537; <ref name=":31" />PMID:22358457 <ref name=":32" />PMID:25043047; <ref name=":33" />PMID:22820256; <ref name=":34" />PMID:26976201 <ref name=":34" />PMID:20823417; <ref name=":35" />PMID:22265402; <ref name=":36" />PMCID:3889646 <ref name=":37" />PMID:16567768; <ref name=":38" />PMID:20940197 |
|- | |- | ||
| | | | ||
| Line 189: | Line 191: | ||
'''Rearrangement:''' idic(17)(p11.2)<br> | '''Rearrangement:''' idic(17)(p11.2)<br> | ||
'''Ploidy changes:''' tetraploidy in 40-50% of Group3/Group4 tumors | '''Ploidy changes:''' tetraploidy in 40-50% of Group3/Group4 tumors | ||
| − | |'''Mutation/Amplification:''' MYC (mainly in infants), OTX2, CDK6, SMARC4A, CTDNEP1, LRP1B, KMT2D<br> | + | |'''Mutation/Amplification:''' [[MYC]] (mainly in infants), [[OTX2]], [[CDK6]], [[SMARC4A]], [[CTDNEP1]], [[LRP1B]], [[KMT2D]]<br> |
| − | '''Fusions:''' PVT1-MYC, PVT1-NDRG1; GFI1/GFI1B structural variants | + | '''Fusions:''' [[PVT1]]-[[MYC]], [[PVT1]]-[[NDRG1]]; [[GFI1]]/[[GFI1B]] structural variants |
| − | |Usually classic histology, ~ 50% are metastatic at time of diagnosis, Not generally observed in adults | + | |Usually classic histology, ~ 50% are metastatic at time of diagnosis, Not generally observed in adults |
| − | |PMID:22832581, PMID:25043047; PMID:24493713 | + | |<ref name=":28" />PMID:22832581, <ref name=":32" />PMID:25043047; <ref name=":29" />PMID:24493713 <ref name=":30" />PMID:22134537; <ref name=":31" />PMID:22358457; <ref name=":33" />PMID:22820256; <ref name=":34" />PMID:26976201; <ref name=":34" />PMID:20823417 <ref name=":35" />PMID:22265402; <ref name=":36" />PMCID:3889646; <ref name=":37" />PMID:16567768 <ref name=":38" />PMID:20940197 |
|- | |- | ||
| | | | ||
| Line 200: | Line 202: | ||
'''Rearrangement:''' idic(17)(p11.2) in >80%<br> | '''Rearrangement:''' idic(17)(p11.2) in >80%<br> | ||
'''Chromothripsis:''' rare, but associated with TP53 loss when observed | '''Chromothripsis:''' rare, but associated with TP53 loss when observed | ||
| − | |'''Mutation:''' TP53, KDM6A, KMT2C <br> | + | |'''Mutation:''' [[TP53]], [[KDM6A]], [[KMT2C]] <br> |
| − | '''Amplification:''' MYCN, CDK4, CDK6, OTX2<br> | + | '''Amplification:''' [[MYCN]], [[CDK4]], [[CDK6]], [[OTX2]]<br> |
| − | '''Rearrangement:''' SNCAIP tandem duplication; GFI1/GFI1B structural variants | + | '''Rearrangement:''' [[SNCAIP]] tandem duplication; [[GFI1]]/[[GFI1B]] structural variants |
| − | |Rarely seen in infants; usually classic histology | + | |Rarely seen in infants; usually classic histology |
| − | |PMID:22832581; PMID:25043047; PMID:24493713 | + | |<ref name=":28" />PMID:22832581; <ref name=":32" />PMID:25043047; <ref name=":29" />PMID:24493713; <ref name=":30" />PMID:22134537; <ref name=":31" />PMID:22358457; <ref name=":33" />PMID:22820256; <ref name=":34" />PMID:26976201; <ref name=":34" />PMID:20823417 <ref name=":35" />PMID:22265402; <ref name=":36" />PMCID:3889646; <ref name=":37" />PMID:16567768 <ref name=":38" />PMID:20940197 |
|- | |- | ||
|Atypical teratoid/rhabdoid tumor (AT/RT) | |Atypical teratoid/rhabdoid tumor (AT/RT) | ||
| | | | ||
|'''Loss:''' 22/22q, though a subset of AT/RT-like tumors retain 22q | |'''Loss:''' 22/22q, though a subset of AT/RT-like tumors retain 22q | ||
| − | |Classic AT/RT: SMARCB1 mutation/deletion/exonic duplication in 98% of tumors<br> | + | |Classic AT/RT: [[SMARCB1]] mutation/deletion/exonic duplication in 98% of tumors<br> |
| − | AT/RT-like tumors: SMARCB1 can be retained (with SMARCA4 mutations)<br> | + | AT/RT-like tumors: [[SMARCB1]] can be retained (with [[SMARCA4]] mutations)<br> |
'''Three molecular classes:'''<br> | '''Three molecular classes:'''<br> | ||
| − | '''TYR:''' ~ 75% show broad 22q loss that includes SMARCB1<br> | + | '''TYR:''' ~ 75% show broad 22q loss that includes [[SMARCB1]]<br> |
| − | '''SHH:''' ~ 50% lack any SMARCB1 mutation; ~ 25% have focal SMARCB1 aberrations<br> | + | '''SHH:''' ~ 50% lack any [[SMARCB1]] mutation; ~ 25% have focal [[SMARCB1]] aberrations<br> |
| − | '''MYC:''' ~ 75% show focal SMARCB1 loss | + | '''MYC:''' ~ 75% show focal [[SMARCB1]] loss |
|Most cases occur before 3 yrs of age<br> | |Most cases occur before 3 yrs of age<br> | ||
TYR subclass: mostly infratentorial<br> | TYR subclass: mostly infratentorial<br> | ||
| Line 223: | Line 225: | ||
|Embryonal tumor with multilayered rosettes, C19MC-altered | |Embryonal tumor with multilayered rosettes, C19MC-altered | ||
| | | | ||
| − | |'''ETMR (incl. ETANTR):''' occasionally polysomy 2 | + | |'''ETMR (incl. ETANTR):''' occasionally polysomy 2 |
|'''ETANTR:''' miRNA cluster C19MC amplification | |'''ETANTR:''' miRNA cluster C19MC amplification | ||
|Occurs mainly in children < 4 yrs old | |Occurs mainly in children < 4 yrs old | ||
| − | | WHO CNS Tumors (2016)<br> | + | |WHO CNS Tumors (2016)<br> |
| − | PMID:24839957; PMID:24470553 PMID:24337497; PMID:22324795 PMID:20407781, PMID:19057917 | + | <ref>{{Cite journal|last=Spence|first=Tara|last2=Sin-Chan|first2=Patrick|last3=Picard|first3=Daniel|last4=Barszczyk|first4=Mark|last5=Hoss|first5=Katharina|last6=Lu|first6=Mei|last7=Kim|first7=Seung-Ki|last8=Ra|first8=Young-Shin|last9=Nakamura|first9=Hideo|date=2014-08|title=CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity|url=https://pubmed.ncbi.nlm.nih.gov/24839957|journal=Acta Neuropathologica|volume=128|issue=2|pages=291–303|doi=10.1007/s00401-014-1291-1|issn=1432-0533|pmc=4159569|pmid=24839957}}</ref>PMID:24839957; <ref>{{Cite journal|last=Gessi|first=Marco|last2=von Bueren|first2=André O.|last3=Treszl|first3=Andras|last4=zur Mühlen|first4=Anja|last5=Hartmann|first5=Wolfgang|last6=Warmuth-Metz|first6=Monika|last7=Rutkowski|first7=Stefan|last8=Pietsch|first8=Torsten|date=2014-07|title=MYCN amplification predicts poor outcome for patients with supratentorial primitive neuroectodermal tumors of the central nervous system|url=https://pubmed.ncbi.nlm.nih.gov/24470553|journal=Neuro-Oncology|volume=16|issue=7|pages=924–932|doi=10.1093/neuonc/not302|issn=1523-5866|pmc=4057132|pmid=24470553}}</ref>PMID:24470553 <ref>{{Cite journal|last=Korshunov|first=Andrey|last2=Sturm|first2=Dominik|last3=Ryzhova|first3=Marina|last4=Hovestadt|first4=Volker|last5=Gessi|first5=Marco|last6=Jones|first6=David T. W.|last7=Remke|first7=Marc|last8=Northcott|first8=Paul|last9=Perry|first9=Arie|date=2014-08|title=Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity|url=https://pubmed.ncbi.nlm.nih.gov/24337497|journal=Acta Neuropathologica|volume=128|issue=2|pages=279–289|doi=10.1007/s00401-013-1228-0|issn=1432-0533|pmc=4102829|pmid=24337497}}</ref>PMID:24337497; <ref>{{Cite journal|last=Nobusawa|first=Sumihito|last2=Yokoo|first2=Hideaki|last3=Hirato|first3=Junko|last4=Kakita|first4=Akiyoshi|last5=Takahashi|first5=Hitoshi|last6=Sugino|first6=Takashi|last7=Tasaki|first7=Kazuhiro|last8=Itoh|first8=Hideaki|last9=Hatori|first9=Tsutomu|date=2012-09|title=Analysis of chromosome 19q13.42 amplification in embryonal brain tumors with ependymoblastic multilayered rosettes|url=https://pubmed.ncbi.nlm.nih.gov/22324795|journal=Brain Pathology (Zurich, Switzerland)|volume=22|issue=5|pages=689–697|doi=10.1111/j.1750-3639.2012.00574.x|issn=1750-3639|pmid=22324795}}</ref>PMID:22324795 <ref>{{Cite journal|last=Korshunov|first=Andrey|last2=Remke|first2=Marc|last3=Gessi|first3=Marco|last4=Ryzhova|first4=Marina|last5=Hielscher|first5=Thomas|last6=Witt|first6=Hendrik|last7=Tobias|first7=Vivienne|last8=Buccoliero|first8=Anna Maria|last9=Sardi|first9=Iacopo|date=2010-08|title=Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes|url=https://pubmed.ncbi.nlm.nih.gov/20407781|journal=Acta Neuropathologica|volume=120|issue=2|pages=253–260|doi=10.1007/s00401-010-0688-8|issn=1432-0533|pmid=20407781}}</ref>PMID:20407781, <ref>{{Cite journal|last=Pfister|first=Stefan|last2=Remke|first2=Marc|last3=Castoldi|first3=Mirco|last4=Bai|first4=Alfa H. C.|last5=Muckenthaler|first5=Martina U.|last6=Kulozik|first6=Andreas|last7=von Deimling|first7=Andreas|last8=Pscherer|first8=Armin|last9=Lichter|first9=Peter|date=2009-04|title=Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes|url=https://pubmed.ncbi.nlm.nih.gov/19057917|journal=Acta Neuropathologica|volume=117|issue=4|pages=457–464|doi=10.1007/s00401-008-0467-y|issn=1432-0533|pmid=19057917}}</ref>PMID:19057917 |
|- | |- | ||
|Embryonal tumor, other | |Embryonal tumor, other | ||
| Line 235: | Line 237: | ||
'''CNS HGNET-MN1 group:''' 16q loss, polysomy 8<br> | '''CNS HGNET-MN1 group:''' 16q loss, polysomy 8<br> | ||
'''CNS HGNET-BCOR group:''' mostly balanced genomes | '''CNS HGNET-BCOR group:''' mostly balanced genomes | ||
| − | |'''CNS NB-FOXR2 group:''' JMJD1C fusions, FOXR2 fusion or deletion<br> | + | |'''CNS NB-FOXR2 group:''' [[JMJD1C]] fusions, [[FOXR2]] fusion or deletion<br> |
| − | '''CNS EFT-CIC group:''' NUTM1 rearrangement/fusion, CIC rearrangement<br> | + | '''CNS EFT-CIC group:''' [[NUTM1]] rearrangement/fusion, [[CIC]] rearrangement<br> |
| − | '''CNS HGNET-MN1 group:''' MN1 rearrangement <br> | + | '''CNS HGNET-MN1 group:''' [[MN1]] rearrangement <br> |
| − | '''CNS HGNET-BCOR group:''' BCOR intragenic tandem duplication | + | '''CNS HGNET-BCOR group:''' [[BCOR]] intragenic tandem duplication |
|Most common in children, but may also occur in adolescents and adults | |Most common in children, but may also occur in adolescents and adults | ||
|WHO CNS Tumors (2016)<br> | |WHO CNS Tumors (2016)<br> | ||
| − | PMID:26919435; PMID:22691720; PMID:22772606 | + | <ref>{{Cite journal|last=Sturm|first=Dominik|last2=Orr|first2=Brent A.|last3=Toprak|first3=Umut H.|last4=Hovestadt|first4=Volker|last5=Jones|first5=David T. W.|last6=Capper|first6=David|last7=Sill|first7=Martin|last8=Buchhalter|first8=Ivo|last9=Northcott|first9=Paul A.|date=2016-02-25|title=New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs|url=https://pubmed.ncbi.nlm.nih.gov/26919435|journal=Cell|volume=164|issue=5|pages=1060–1072|doi=10.1016/j.cell.2016.01.015|issn=1097-4172|pmc=5139621|pmid=26919435}}</ref>PMID:26919435; <ref>{{Cite journal|last=Picard|first=Daniel|last2=Miller|first2=Suzanne|last3=Hawkins|first3=Cynthia E.|last4=Bouffet|first4=Eric|last5=Rogers|first5=Hazel A.|last6=Chan|first6=Tiffany S. Y.|last7=Kim|first7=Seung-Ki|last8=Ra|first8=Young-Shin|last9=Fangusaro|first9=Jason|date=2012-08|title=Markers of survival and metastatic potential in childhood CNS primitive neuro-ectodermal brain tumours: an integrative genomic analysis|url=https://pubmed.ncbi.nlm.nih.gov/22691720|journal=The Lancet. Oncology|volume=13|issue=8|pages=838–848|doi=10.1016/S1470-2045(12)70257-7|issn=1474-5488|pmc=3615440|pmid=22691720}}</ref>PMID:22691720; <ref>{{Cite journal|last=von Bueren|first=André O.|last2=Gerss|first2=Joachim|last3=Hagel|first3=Christian|last4=Cai|first4=Haoyang|last5=Remke|first5=Marc|last6=Hasselblatt|first6=Martin|last7=Feuerstein|first7=Burt G.|last8=Pernet|first8=Sarah|last9=Delattre|first9=Olivier|date=2012-09|title=DNA copy number alterations in central primitive neuroectodermal tumors and tumors of the pineal region: an international individual patient data meta-analysis|url=https://pubmed.ncbi.nlm.nih.gov/22772606|journal=Journal of Neuro-Oncology|volume=109|issue=2|pages=415–423|doi=10.1007/s11060-012-0911-7|issn=1573-7373|pmid=22772606}}</ref>PMID:22772606 |
|- | |- | ||
|'''CHOROID PLEXUS TUMORS (CPT)''' | |'''CHOROID PLEXUS TUMORS (CPT)''' | ||
| Line 248: | Line 250: | ||
'''Loss:''' rare, no recurrent losses | '''Loss:''' rare, no recurrent losses | ||
|No diagnostic mutations/events | |No diagnostic mutations/events | ||
| − | |CPP and aCPP likely belong to same molecularly defined entity; CPP is a diagnostic feature of Aircardi syndrome | + | |CPP and aCPP likely belong to same molecularly defined entity; CPP is a diagnostic feature of Aircardi syndrome |
|WHO CNS Tumors (2016)<br> | |WHO CNS Tumors (2016)<br> | ||
| − | PMID:23172371; PMID:25575132; PMID:25336695 PMID:11891207 | + | <ref>{{Cite journal|last=Safaee|first=Michael|last2=Oh|first2=Michael C.|last3=Bloch|first3=Orin|last4=Sun|first4=Matthew Z.|last5=Kaur|first5=Gurvinder|last6=Auguste|first6=Kurtis I.|last7=Tihan|first7=Tarik|last8=Parsa|first8=Andrew T.|date=2013-03|title=Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis|url=https://pubmed.ncbi.nlm.nih.gov/23172371|journal=Neuro-Oncology|volume=15|issue=3|pages=255–267|doi=10.1093/neuonc/nos289|issn=1523-5866|pmc=3578480|pmid=23172371}}</ref>PMID:23172371; <ref name=":39">{{Cite journal|last=Japp|first=Anna Sophia|last2=Gessi|first2=Marco|last3=Messing-Jünger|first3=Martina|last4=Denkhaus|first4=Dorota|last5=Zur Mühlen|first5=Anja|last6=Wolff|first6=Johannes Ernst|last7=Hartung|first7=Stefan|last8=Kordes|first8=Uwe|last9=Klein-Hitpass|first9=Ludger|date=2015-02|title=High-resolution genomic analysis does not qualify atypical plexus papilloma as a separate entity among choroid plexus tumors|url=https://pubmed.ncbi.nlm.nih.gov/25575132|journal=Journal of Neuropathology and Experimental Neurology|volume=74|issue=2|pages=110–120|doi=10.1097/NEN.0000000000000154|issn=1554-6578|pmid=25575132}}</ref>PMID:25575132; <ref name=":40">{{Cite journal|last=Merino|first=Diana M.|last2=Shlien|first2=Adam|last3=Villani|first3=Anita|last4=Pienkowska|first4=Malgorzata|last5=Mack|first5=Stephen|last6=Ramaswamy|first6=Vijay|last7=Shih|first7=David|last8=Tatevossian|first8=Ruth|last9=Novokmet|first9=Ana|date=2015-01-01|title=Molecular characterization of choroid plexus tumors reveals novel clinically relevant subgroups|url=https://pubmed.ncbi.nlm.nih.gov/25336695|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=21|issue=1|pages=184–192|doi=10.1158/1078-0432.CCR-14-1324|issn=1557-3265|pmid=25336695}}</ref>PMID:25336695 <ref>{{Cite journal|last=Rickert|first=Christian H.|last2=Wiestler|first2=Otmar D.|last3=Paulus|first3=Werner|date=2002-03|title=Chromosomal imbalances in choroid plexus tumors|url=https://pubmed.ncbi.nlm.nih.gov/11891207|journal=The American Journal of Pathology|volume=160|issue=3|pages=1105–1113|doi=10.1016/S0002-9440(10)64931-0|issn=0002-9440|pmc=1867193|pmid=11891207}}</ref>PMID:11891207 |
|- | |- | ||
| | | | ||
| Line 257: | Line 259: | ||
'''Gain:''' 1, 7, 12, 20 in > 80% of hyperdiploid CPCs<br> | '''Gain:''' 1, 7, 12, 20 in > 80% of hyperdiploid CPCs<br> | ||
'''Loss:''' 3 (in all hypodiploid CPC), 6, 11, 12q, 16, 22 | '''Loss:''' 3 (in all hypodiploid CPC), 6, 11, 12q, 16, 22 | ||
| − | |'''Mutation:''' TP53 in > 50%<br> | + | |'''Mutation:''' [[TP53]] in > 50%<br> |
| − | '''Amplification:''' PDGFRB | + | '''Amplification:''' [[PDGFRB]] |
| − | |80% occur in children; associated with Li-Fraumeni syndrome; Lack of SMARCB1/SMARCA4 aberrations can be used to distinguish CPC from AT/RT | + | |80% occur in children; associated with Li-Fraumeni syndrome; Lack of SMARCB1/SMARCA4 aberrations can be used to distinguish CPC from AT/RT |
| − | |PMID:24478045; PMID:21990040; PMID:25575132; PMID:18157090; PMID:25336695 | + | |<ref>{{Cite journal|last=Ruland|first=Vincent|last2=Hartung|first2=Stefan|last3=Kordes|first3=Uwe|last4=Wolff|first4=Johannes E.|last5=Paulus|first5=Werner|last6=Hasselblatt|first6=Martin|date=2014-05|title=Choroid plexus carcinomas are characterized by complex chromosomal alterations related to patient age and prognosis|url=https://pubmed.ncbi.nlm.nih.gov/24478045|journal=Genes, Chromosomes & Cancer|volume=53|issue=5|pages=373–380|doi=10.1002/gcc.22148|issn=1098-2264|pmid=24478045}}</ref>PMID:24478045; <ref>{{Cite journal|last=Gozali|first=Alexa E.|last2=Britt|first2=Barbara|last3=Shane|first3=Lisa|last4=Gonzalez|first4=Ignacio|last5=Gilles|first5=Floyd|last6=McComb|first6=J. Gordon|last7=Krieger|first7=Mark D.|last8=Lavey|first8=Robert S.|last9=Shlien|first9=Adam|date=2012-06|title=Choroid plexus tumors; management, outcome, and association with the Li-Fraumeni syndrome: the Children's Hospital Los Angeles (CHLA) experience, 1991-2010|url=https://pubmed.ncbi.nlm.nih.gov/21990040|journal=Pediatric Blood & Cancer|volume=58|issue=6|pages=905–909|doi=10.1002/pbc.23349|issn=1545-5017|pmid=21990040}}</ref>PMID:21990040; <ref name=":39" />PMID:25575132; <ref>{{Cite journal|last=Nupponen|first=Nina N.|last2=Paulsson|first2=Janna|last3=Jeibmann|first3=Astrid|last4=Wrede|first4=Brigitte|last5=Tanner|first5=Minna|last6=Wolff|first6=Johannes E. A.|last7=Paulus|first7=Werner|last8=Ostman|first8=Arne|last9=Hasselblatt|first9=Martin|date=2008-03|title=Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas|url=https://pubmed.ncbi.nlm.nih.gov/18157090|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=21|issue=3|pages=265–270|doi=10.1038/modpathol.3800989|issn=0893-3952|pmid=18157090}}</ref>PMID:18157090; <ref name=":40" />PMID:25336695 |
| + | |} | ||
| + | |||
| + | '''Table 2:''' Adult CNS Tumors. CGC CNS Workgroup 2015-2018. Table derived from Neill et al., 2020 [[https://pubmed.ncbi.nlm.nih.gov/32203924/ PMID: 32203924]] with permission from Cancer Genetics. | ||
| + | {| class="wikitable" | ||
| + | |- | ||
| + | !TUMOR | ||
| + | !SUBTYPES | ||
| + | !BROAD ABERRATIONS (>10Mb) | ||
| + | !FOCAL ABERRATIONS (<10Mb) | ||
| + | !CLINICAL FEATURES | ||
| + | !REFERENCES | ||
| + | |- | ||
| + | |'''GLIOMAS''' | ||
| + | | | ||
| + | | | ||
| + | | | ||
| + | | | ||
| + | | | ||
| + | |- | ||
| + | |Low grade gliomas, WHO grade I-II | ||
| + | |Pilocytic astrocytoma | ||
| + | |'''Gain:''' 5, 7, 6, 11<br> | ||
| + | '''Loss:''' 1, 2, 3, 13, 14, 16, 17, 19 | ||
| + | |'''Fusion:''' [[KIAA1549]]-[[BRAF]] fusion (via 3'[[BRAF]] duplication), other [[BRAF]] partners reported; NTRK fusions (rare)<br> | ||
| + | '''Mutation:''' [[FGFR1]] | ||
| + | |Aneuploidy is more predominant in adult PA; Infratentorial tumors are more likely to have BRAF fusions/dup and be wildtype for BRAF mutations; Extra-cerebellar tumors are more likely to be BRAF V600E+, but negative for fusion; Surgical resection can be curative | ||
| + | |<ref>{{Cite journal|last=Theeler|first=Brett J.|last2=Ellezam|first2=Benjamin|last3=Sadighi|first3=Zsila S.|last4=Mehta|first4=Vidya|last5=Tran|first5=M. Diep|last6=Adesina|first6=Adekunle M.|last7=Bruner|first7=Janet M.|last8=Puduvalli|first8=Vinay K.|date=2014-06|title=Adult pilocytic astrocytomas: clinical features and molecular analysis|url=https://pubmed.ncbi.nlm.nih.gov/24470550|journal=Neuro-Oncology|volume=16|issue=6|pages=841–847|doi=10.1093/neuonc/not246|issn=1523-5866|pmc=4022218|pmid=24470550}}</ref>PMID: 24470550; <ref name=":2" />PMID:26378811; <ref name=":1" />PMID: 25664944; <ref>{{Cite journal|last=Strowd|first=Roy E.|last2=Rodriguez|first2=Fausto J.|last3=McLendon|first3=Roger E.|last4=Vredenburgh|first4=James J.|last5=Chance|first5=Aaron B.|last6=Jallo|first6=George|last7=Olivi|first7=Alessandro|last8=Ahn|first8=Edward S.|last9=Blakeley|first9=Jaishri O.|date=2016-06|title=Histologically benign, clinically aggressive: Progressive non-optic pathway pilocytic astrocytomas in adults with NF1|url=https://pubmed.ncbi.nlm.nih.gov/26992069|journal=American Journal of Medical Genetics. Part A|volume=170|issue=6|pages=1455–1461|doi=10.1002/ajmg.a.37622|issn=1552-4833|pmc=4938896|pmid=26992069}}</ref>PMID:26992069 | ||
| + | |- | ||
| + | | | ||
| + | |Pleomorphic xanthoastrocytoma (PXA) | ||
| + | |'''Gain:''' 7, 2, 5, 21, 20, 12, 15<br> | ||
| + | '''Loss:''' monosomy 9 / 9p deletion most common, 22, 14, 13, 10<br> | ||
| + | '''CN-LOH:''' 9p, 22 | ||
| + | |'''Loss:''' homozygous loss [[CDKN2A]]/[[CDKN2B]]<br> | ||
| + | Mutation: [[BRAF]] V600E | ||
| + | |Adults and pediatric tumors show similar CNVs; CDKN2A/CDKN2B loss may correlate with anaplastic histology | ||
| + | |<ref name=":41">{{Cite journal|last=Chappé|first=Céline|last2=Padovani|first2=Laetitia|last3=Scavarda|first3=Didier|last4=Forest|first4=Fabien|last5=Nanni-Metellus|first5=Isabelle|last6=Loundou|first6=Anderson|last7=Mercurio|first7=Sandy|last8=Fina|first8=Frédéric|last9=Lena|first9=Gabriel|date=2013-09|title=Dysembryoplastic neuroepithelial tumors share with pleomorphic xanthoastrocytomas and gangliogliomas BRAF(V600E) mutation and expression|url=https://pubmed.ncbi.nlm.nih.gov/23442159|journal=Brain Pathology (Zurich, Switzerland)|volume=23|issue=5|pages=574–583|doi=10.1111/bpa.12048|issn=1750-3639|pmid=23442159}}</ref>PMID:23442159; <ref>{{Cite journal|last=Vaubel|first=Rachael A.|last2=Caron|first2=Alissa A.|last3=Yamada|first3=Seiji|last4=Decker|first4=Paul A.|last5=Eckel Passow|first5=Jeanette E.|last6=Rodriguez|first6=Fausto J.|last7=Nageswara Rao|first7=Amulya A.|last8=Lachance|first8=Daniel|last9=Parney|first9=Ian|date=2018-03|title=Recurrent copy number alterations in low-grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation|url=https://pubmed.ncbi.nlm.nih.gov/28181325|journal=Brain Pathology (Zurich, Switzerland)|volume=28|issue=2|pages=172–182|doi=10.1111/bpa.12495|issn=1750-3639|pmc=5807227|pmid=28181325}}</ref>PMID:28181325 | ||
| + | |- | ||
| + | | | ||
| + | |Ganglioglioma | ||
| + | |'''Gain:''' polysomy 5, polysomy 7, 10p<br> | ||
| + | '''Loss:''' 1p loss, monosomy (with focal CDKN2A loss) | ||
| + | |'''Mutation:''' [[BRAF]] V600E, [[TSC1]], [[TSC2]], [[FGFR1]], [[FGFR2]], [[KRAS]] | ||
| + | |Generally indolent tumors; surgical resection can be curative | ||
| + | |<ref name=":41" />PMID:23442159; <ref>{{Cite journal|last=Prabowo|first=Avanita S.|last2=van Thuijl|first2=Hinke Foka|last3=Scheinin|first3=Ilari|last4=Sie|first4=Daoud|last5=van Essen|first5=Hendrik F.|last6=Iyer|first6=Anand M.|last7=Spliet|first7=Wim G. M.|last8=Ferrier|first8=Cyrille H.|last9=van Rijen|first9=Peter C.|date=2015-10|title=Landscape of chromosomal copy number aberrations in gangliogliomas and dysembryoplastic neuroepithelial tumours|url=https://pubmed.ncbi.nlm.nih.gov/25764012|journal=Neuropathology and Applied Neurobiology|volume=41|issue=6|pages=743–755|doi=10.1111/nan.12235|issn=1365-2990|pmid=25764012}}</ref>PMID:25764012; <ref name=":7" />PMID:29880043 | ||
| + | |- | ||
| + | | | ||
| + | |Angiocentric glioma | ||
| + | |'''Loss:''' 6q24-q25 | ||
| + | |'''Fusion:''' [[MYB]]-[[QKI]] rearrangement/deletion (classic histology)<br> | ||
| + | '''Rearrangement:''' [[MYB]] alone (atypical histology)<br> | ||
| + | '''Amplification:''' [[MYB]] (atypical histology) | ||
| + | |Generally indolent tumors; surgical resection can be curative | ||
| + | |<ref name=":5" />PMID:26829751 | ||
| + | |- | ||
| + | | | ||
| + | |Dysembryoplastic neuroepithelial tumor (DNET) | ||
| + | |No specific changes | ||
| + | |'''Mutation:''' intragenic duplication or mutation [[FGFR1]]; [[BRAF]] V600E | ||
| + | |Rare in adults; Benign with excellent prognosis even with subtotal resection | ||
| + | |<ref>{{Cite journal|last=Rivera|first=Barbara|last2=Gayden|first2=Tenzin|last3=Carrot-Zhang|first3=Jian|last4=Nadaf|first4=Javad|last5=Boshari|first5=Talia|last6=Faury|first6=Damien|last7=Zeinieh|first7=Michele|last8=Blanc|first8=Romeo|last9=Burk|first9=David L.|date=2016-06|title=Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors|url=https://pubmed.ncbi.nlm.nih.gov/26920151|journal=Acta Neuropathologica|volume=131|issue=6|pages=847–863|doi=10.1007/s00401-016-1549-x|issn=1432-0533|pmc=5039033|pmid=26920151}}</ref>PMID:26920151; <ref name=":41" />PMID:23442159; <ref>{{Cite journal|last=Thom|first=Maria|last2=Toma|first2=Ahmed|last3=An|first3=Shu|last4=Martinian|first4=Lillian|last5=Hadjivassiliou|first5=George|last6=Ratilal|first6=Bernardo|last7=Dean|first7=Andrew|last8=McEvoy|first8=Andrew|last9=Sisodiya|first9=Sanjay M.|date=2011-10|title=One hundred and one dysembryoplastic neuroepithelial tumors: an adult epilepsy series with immunohistochemical, molecular genetic, and clinical correlations and a review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/21937911|journal=Journal of Neuropathology and Experimental Neurology|volume=70|issue=10|pages=859–878|doi=10.1097/NEN.0b013e3182302475|issn=1554-6578|pmid=21937911}}</ref>PMID:21937911 | ||
| + | |- | ||
| + | | | ||
| + | |Rosette forming glioneuronal tumor | ||
| + | |'''Gain:'''1q , 7, 9, 16<br> | ||
| + | '''Loss:''' 1p<br> | ||
| + | '''Amplification:''' 9q34.2, 19p13.3 | ||
| + | |'''Fusion:''' [[KIAA1549]]-[[BRAF]] fusion (via 3'[[BRAF]] duplication)<br> | ||
| + | '''Mutation:''' [[PIK3CA]], [[FGFR1]]<br> | ||
| + | '''Amplification:''' [[SBNO2]] | ||
| + | |Generally indolent tumors; surgical resection can be curative | ||
| + | |<ref>{{Cite journal|last=Kitamura|first=Yohei|last2=Komori|first2=Takashi|last3=Shibuya|first3=Makoto|last4=Ohara|first4=Kentaro|last5=Saito|first5=Yuko|last6=Hayashi|first6=Saeko|last7=Sasaki|first7=Aya|last8=Nakagawa|first8=Eiji|last9=Tomio|first9=Ryosuke|date=2018-01|title=Comprehensive genetic characterization of rosette-forming glioneuronal tumors: independent component analysis by tissue microdissection|url=https://pubmed.ncbi.nlm.nih.gov/27893178|journal=Brain Pathology (Zurich, Switzerland)|volume=28|issue=1|pages=87–93|doi=10.1111/bpa.12468|issn=1750-3639|pmid=27893178}}</ref>PMID:27893178; <ref>{{Cite journal|last=Bidinotto|first=Lucas Tadeu|last2=Scapulatempo-Neto|first2=Cristovam|last3=Mackay|first3=Alan|last4=de Almeida|first4=Gisele Caravina|last5=Scheithauer|first5=Bernd Walter|last6=Berardinelli|first6=Gustavo Noriz|last7=Torrieri|first7=Raul|last8=Clara|first8=Carlos Afonso|last9=Feltrin|first9=Leonir Terezinha|date=2015|title=Molecular Profiling of a Rare Rosette-Forming Glioneuronal Tumor Arising in the Spinal Cord|url=https://pubmed.ncbi.nlm.nih.gov/26371886|journal=PloS One|volume=10|issue=9|pages=e0137690|doi=10.1371/journal.pone.0137690|issn=1932-6203|pmc=4570813|pmid=26371886}}</ref>PMID:26371886 | ||
| + | |- | ||
| + | |Infiltrating Gliomas | ||
| + | |Diffuse astrocytoma/anaplastic Astrocytoma, WHO grade II/III, IDH mutant | ||
| + | |'''Gain:''' 4q, 7q, 8q24, 12q<br> | ||
| + | '''Loss:''' 9p, 19q (without 1p) | ||
| + | |'''Gain:''' [[MYC]] <br> | ||
| + | '''Loss:''' [[CDKN2A]]/[[CDKN2B]], [[PML]]15q22 | ||
| + | |Better prognosis than IDH wildtype astrocytoma; Progression to grade IV will often involves loss of 10q, gain of CDK4, CDK6, and cyclin E2, and an increase in copy number alterations. | ||
| + | |<ref name=":9" />PMID:26824661; <ref name=":42">{{Cite journal|last=Eckel-Passow|first=Jeanette E.|last2=Lachance|first2=Daniel H.|last3=Molinaro|first3=Annette M.|last4=Walsh|first4=Kyle M.|last5=Decker|first5=Paul A.|last6=Sicotte|first6=Hugues|last7=Pekmezci|first7=Melike|last8=Rice|first8=Terri|last9=Kosel|first9=Matt L.|date=2015-06-25|title=Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors|url=https://pubmed.ncbi.nlm.nih.gov/26061753|journal=The New England Journal of Medicine|volume=372|issue=26|pages=2499–2508|doi=10.1056/NEJMoa1407279|issn=1533-4406|pmc=4489704|pmid=26061753}}</ref>PMID:26061753; <ref name=":43">{{Cite journal|last=Neill|first=Stewart G.|last2=Fisher|first2=Kevin E.|date=2014-09-XX|title=Section III: molecular diagnostics in neuro-oncology|url=https://pubmed.ncbi.nlm.nih.gov/25263767|journal=Current Problems in Cancer|volume=38|issue=5|pages=175–179|doi=10.1016/j.currproblcancer.2014.08.006|issn=1535-6345|pmid=25263767}}</ref>PMID:25263767 <ref name=":44">{{Cite journal|last=Ellison|first=David W.|date=2015-06-25|title=Multiple Molecular Data Sets and the Classification of Adult Diffuse Gliomas|url=https://pubmed.ncbi.nlm.nih.gov/26061754|journal=The New England Journal of Medicine|volume=372|issue=26|pages=2555–2557|doi=10.1056/NEJMe1506813|issn=1533-4406|pmid=26061754}}</ref>PMID:26061754; <ref name=":45">{{Cite journal|last=Park|first=Sung-Hye|last2=Won|first2=Jaekyung|last3=Kim|first3=Seong-Ik|last4=Lee|first4=Yujin|last5=Park|first5=Chul-Kee|last6=Kim|first6=Seung-Ki|last7=Choi|first7=Seung-Hong|date=2017-05|title=Molecular Testing of Brain Tumor|url=https://pubmed.ncbi.nlm.nih.gov/28535583|journal=Journal of Pathology and Translational Medicine|volume=51|issue=3|pages=205–223|doi=10.4132/jptm.2017.03.08|issn=2383-7837|pmc=5445205|pmid=28535583}}</ref>PMID:28535583; <ref name=":46">{{Cite journal|last=Cohen|first=Adam|last2=Sato|first2=Mariko|last3=Aldape|first3=Kenneth|last4=Mason|first4=Clinton C.|last5=Alfaro-Munoz|first5=Kristin|last6=Heathcock|first6=Lindsey|last7=South|first7=Sarah T.|last8=Abegglen|first8=Lisa M.|last9=Schiffman|first9=Joshua D.|date=2015-06-20|title=DNA copy number analysis of Grade II-III and Grade IV gliomas reveals differences in molecular ontogeny including chromothripsis associated with IDH mutation status|url=https://pubmed.ncbi.nlm.nih.gov/26091668|journal=Acta Neuropathologica Communications|volume=3|pages=34|doi=10.1186/s40478-015-0213-3|issn=2051-5960|pmc=4474351|pmid=26091668}}</ref>PMID:26091668 <ref>{{Cite journal|last=Olar|first=Adriana|last2=Wani|first2=Khalida M.|last3=Alfaro-Munoz|first3=Kristin D.|last4=Heathcock|first4=Lindsey E.|last5=van Thuijl|first5=Hinke F.|last6=Gilbert|first6=Mark R.|last7=Armstrong|first7=Terri S.|last8=Sulman|first8=Erik P.|last9=Cahill|first9=Daniel P.|date=2015-04|title=IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas|url=https://pubmed.ncbi.nlm.nih.gov/25701198|journal=Acta Neuropathologica|volume=129|issue=4|pages=585–596|doi=10.1007/s00401-015-1398-z|issn=1432-0533|pmc=4369189|pmid=25701198}}</ref>PMID: 25701198; <ref>{{Cite journal|last=Lhotska|first=Halka|last2=Zemanova|first2=Zuzana|last3=Cechova|first3=Hana|last4=Ransdorfova|first4=Sarka|last5=Svobodova|first5=Karla|last6=Kramar|first6=Filip|last7=Krejcik|first7=Zdenek|last8=Michalova|first8=Kyra|date=2016|title=Primary and recurrent diffuse astrocytomas: genomic profile comparison reveals acquisition of biologically relevant aberrations|url=https://pubmed.ncbi.nlm.nih.gov/26865861|journal=Molecular Cytogenetics|volume=9|pages=13|doi=10.1186/s13039-016-0222-3|issn=1755-8166|pmc=4748601|pmid=26865861}}</ref>PMID:26865861; <ref name=":13" />PMID:29687258 | ||
| + | |- | ||
| + | | | ||
| + | |Diffuse astrocytoma/anaplastic astrocytoma, WHO grade II/III, IDH wild-type | ||
| + | |'''Gain:''' 7, 19<br> | ||
| + | '''Loss:''' 4, 9p 10<br> | ||
| + | '''Amplification:''' [[EGFR]], [[MDM4]], [[CDK4]] | ||
| + | |'''Loss:''' homozygous [[CDKN2A]]/[[CDKN2B]]<br> | ||
| + | '''Mutation:''' [[EGFR]], [[NF1]], [[PTEN]]<br> | ||
| + | '''Amplification:''' [[EGFR]], [[MDM4]], [[CDK4]] | ||
| + | |Poor prognosis with similar abnormalities to glioblastoma | ||
| + | |<ref name=":44" />PMID:26061754; <ref name=":9" />PMID:26824661; <ref name=":45" />PMID:28535583 <ref name=":46" />PMID:26091668; <ref>{{Cite journal|last=Qaddoumi|first=Ibrahim|last2=Orisme|first2=Wilda|last3=Wen|first3=Ji|last4=Santiago|first4=Teresa|last5=Gupta|first5=Kirti|last6=Dalton|first6=James D.|last7=Tang|first7=Bo|last8=Haupfear|first8=Kelly|last9=Punchihewa|first9=Chandanamali|date=2016-06|title=Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology|url=https://pubmed.ncbi.nlm.nih.gov/26810070|journal=Acta Neuropathologica|volume=131|issue=6|pages=833–845|doi=10.1007/s00401-016-1539-z|issn=1432-0533|pmc=4866893|pmid=26810070}}</ref>PMID:26810070 | ||
| + | |- | ||
| + | | | ||
| + | |Oligodendroglioma/anaplastic oligodendroglioma, WHO grade II/III, IDH mutant | ||
| + | |'''Rearrangement:''' der(1;19)(q10;p10) leads to 1p/19q co-deletion<br> | ||
| + | '''Loss:''' 1p/19q, 9p, 14q, less frequent 4, 18q | ||
| + | |'''Gain:''' [[MYC]]<br> | ||
| + | '''Loss:''' [[MAX]] (14q), [[FBXW7]], [[CDKN2A]]/[[CDKN2B]]<br> | ||
| + | '''Mutation:''' [[FUBP1]], [[CIC]], IDH, [[TERT]], [[NOTCH1]], [[PIK3CA]] or [[PIK3R1]] | ||
| + | |Activation of MYC pathway is often seen with loss of 9p (CDKN2A/B), and 14q (MAX gene) and is reported to have a worse prognosis | ||
| + | |<ref>{{Cite journal|last=Kamoun|first=Aurélie|last2=Idbaih|first2=Ahmed|last3=Dehais|first3=Caroline|last4=Elarouci|first4=Nabila|last5=Carpentier|first5=Catherine|last6=Letouzé|first6=Eric|last7=Colin|first7=Carole|last8=Mokhtari|first8=Karima|last9=Jouvet|first9=Anne|date=2016-04-19|title=Integrated multi-omics analysis of oligodendroglial tumours identifies three subgroups of 1p/19q co-deleted gliomas|url=https://pubmed.ncbi.nlm.nih.gov/27090007|journal=Nature Communications|volume=7|pages=11263|doi=10.1038/ncomms11263|issn=2041-1723|pmc=4838899|pmid=27090007}}</ref>PMID:27090007; <ref name=":42" />PMID:26061753; <ref name=":43" />PMID:25263767 <ref name=":44" />PMID:26061754; <ref>{{Cite journal|last=Alentorn|first=Agustí|last2=van Thuijl|first2=Hinke F.|last3=Marie|first3=Yannick|last4=Alshehhi|first4=Hussa|last5=Carpentier|first5=Catherine|last6=Boisselier|first6=Blandine|last7=Laigle-Donadey|first7=Florence|last8=Mokhtari|first8=Karima|last9=Scheinin|first9=Ilari|date=2014-03|title=Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas|url=https://pubmed.ncbi.nlm.nih.gov/24335697|journal=Neuro-Oncology|volume=16|issue=3|pages=400–408|doi=10.1093/neuonc/not227|issn=1523-5866|pmc=3922518|pmid=24335697}}</ref>PMID:24335697; <ref name=":1" />PMID:25664944; <ref>{{Cite journal|last=Rice|first=Terri|last2=Lachance|first2=Daniel H.|last3=Molinaro|first3=Annette M.|last4=Eckel-Passow|first4=Jeanette E.|last5=Walsh|first5=Kyle M.|last6=Barnholtz-Sloan|first6=Jill|last7=Ostrom|first7=Quinn T.|last8=Francis|first8=Stephen S.|last9=Wiemels|first9=Joseph|date=2016-03|title=Understanding inherited genetic risk of adult glioma - a review|url=https://pubmed.ncbi.nlm.nih.gov/26941959|journal=Neuro-Oncology Practice|volume=3|issue=1|pages=10–16|doi=10.1093/nop/npv026|issn=2054-2577|pmc=4774334|pmid=26941959}}</ref>PMID:26941959; <ref name=":9" />PMID:26824661 <ref name=":8" />PMID:26061751 | ||
| + | |- | ||
| + | | | ||
| + | |Glioblastoma , grade IV, IDH mutant | ||
| + | |'''Gain:''' 1/1q, 6p<br> | ||
| + | '''Loss:''' 3p, 10, 13, 14, 15, 22 (3, 4q, 19q, 16p, 21q, 5p seen in age <40)<br> | ||
| + | '''Amplification:''' [[CDK6]], cyclin E2 ([[CCNE2]]), [[CDK4]], [[MET]]<br> | ||
| + | '''Chromothripsis''' | ||
| + | |'''Gain or Amplification:''' [[CDK4]], [[CDK6]], cyclin E2 ([[CCNE2]])<br> | ||
| + | '''Loss:''' [[PTEN]] | ||
| + | |About 10% of glioblastomas; correspond closely to secondary glioblastoma with history of prior glioma. These cases often involve loss of 10q , gain of CDK4, CDK6, cyclin E2, and increase in copy number alterations. | ||
| + | |<ref name=":44" />PMID:26061754; <ref name=":15" />PMID:25754088; <ref name=":45" />PMID:28535583 <ref name=":47">{{Cite journal|last=Geisenberger|first=Christoph|last2=Mock|first2=Andreas|last3=Warta|first3=Rolf|last4=Rapp|first4=Carmen|last5=Schwager|first5=Christian|last6=Korshunov|first6=Andrey|last7=Nied|first7=Ann-Katrin|last8=Capper|first8=David|last9=Brors|first9=Benedikt|date=2015-09|title=Molecular profiling of long-term survivors identifies a subgroup of glioblastoma characterized by chromosome 19/20 co-gain|url=https://pubmed.ncbi.nlm.nih.gov/25931051|journal=Acta Neuropathologica|volume=130|issue=3|pages=419–434|doi=10.1007/s00401-015-1427-y|issn=1432-0533|pmid=25931051}}</ref>PMID:25931051; <ref name=":46" />PMID:26091668; <ref name=":0" />PMID:25461780; <ref name=":48">{{Cite journal|last=Louis|first=David N.|last2=Perry|first2=Arie|last3=Reifenberger|first3=Guido|last4=von Deimling|first4=Andreas|last5=Figarella-Branger|first5=Dominique|last6=Cavenee|first6=Webster K.|last7=Ohgaki|first7=Hiroko|last8=Wiestler|first8=Otmar D.|last9=Kleihues|first9=Paul|date=2016-06|title=The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary|url=https://pubmed.ncbi.nlm.nih.gov/27157931|journal=Acta Neuropathologica|volume=131|issue=6|pages=803–820|doi=10.1007/s00401-016-1545-1|issn=1432-0533|pmid=27157931}}</ref>PMID:27157931; <ref name=":14" />PMID:25727226; <ref>{{Cite journal|last=Liu|first=Qun|last2=Liu|first2=Yuexin|last3=Li|first3=Wenliang|last4=Wang|first4=Xiaoguang|last5=Sawaya|first5=Raymond|last6=Lang|first6=Frederick F.|last7=Yung|first7=W. K. Alfred|last8=Chen|first8=Kexin|last9=Fuller|first9=Gregory N.|date=2015-10|title=Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma|url=https://pubmed.ncbi.nlm.nih.gov/26323991|journal=Acta Neuropathologica|volume=130|issue=4|pages=587–597|doi=10.1007/s00401-015-1470-8|issn=1432-0533|pmc=4776337|pmid=26323991}}</ref>PMID:26323991 <ref name=":8" />PMID:26061751; <ref name=":13" />PMID:29687258 | ||
| + | |- | ||
| + | | | ||
| + | |Glioblastoma , grade IV, IDH wildtype | ||
| + | |'''Loss:''' 4, 9p, 10, 13, 14, 15, 22 , (3, 4q, 19q, 16p, 21q, 5p loss in age <40)<br> | ||
| + | '''Gain:''' 7, 19, 20 (1q, 12p, 11q, 9q, 4, 10p gain in age <40) <br> | ||
| + | '''Amplification:''' [[EGFR]], [[MDM4]], [[CDK4]], [[MET]] | ||
| + | |'''Loss:''' homozygous [[CDKN2A]]/[[CDKN2B]], [[PTEN]], [[RB1]]<br> | ||
| + | '''Mutation:''' [[TERT]], [[EGFR]], [[PTEN]], [[NF1]], [[RB1]], [[PIK3CA]] or [[PIK3R1]], [[TP53]]<br> | ||
| + | '''Amplification:''' [[EGFR]], [[MDM4]], [[MDM2]], [[CDK4]], [[PDGFRA]], [[MET]] | ||
| + | |Overall poor prognosis. Gain of 19q, amplification of EGFR, and homozygous loss of CDKN2A are seen primarily in patients over age 40. Co-gain of 19 and 20 may be associated with longer survival. | ||
| + | |<ref name=":44" />PMID:26061754; <ref name=":15" />PMID:25754088; <ref name=":45" />PMID:28535583 <ref name=":47" />PMID:25931051; <ref name=":46" />PMID:26091668; <ref name=":0" />PMID:25461780; <ref name=":48" />PMID:27157931; <ref name=":14" />PMID:25727226; <ref name=":8" />PMID:26061751 | ||
| + | |- | ||
| + | |'''MENINGIOMA''' | ||
| + | |- | ||
| + | | | ||
| + | |Grade 1 | ||
| + | |No copy number changes in 44%<br> | ||
| + | '''Gain:''' multiple polysomies, 5<br> | ||
| + | '''Loss:''' 22/22q- common as sole aberration <br> | ||
| + | '''CN-LOH:''' 1p, 14q | ||
| + | |'''Loss:''' [[NF2]], [[CDKN2A]], [[PTEN]]<br> | ||
| + | '''Mutation:''' [[NF2]], [[PI3K]], [[SMO]], [[AKT1]], [[KLF4]], [[TRAF7]], [[TERT]], [[ARID1A]] | ||
| + | |Array findings characteristic of higher grade tumors when histology supports lower grade may suggest increased likelihood of recurrence. Polysomy, particularly involving chromosome 5, are seen in angiomatous meningiomas. LOH 1p and/or LOH 1p/14q correlated with anaplastic transformation. | ||
| + | |<ref name=":24" />PMID:23528542; <ref name=":49">{{Cite journal|last=Och|first=Waldemar|last2=Szmuda|first2=Tomasz|last3=Sikorska|first3=Beata|last4=Springer|first4=Janusz|last5=Jaskólski|first5=Dariusz|last6=Zakrzewska|first6=Magdalena|last7=Liberski|first7=Paweł P.|date=2016-11-XX|title=Recurrence-associated chromosomal anomalies in meningiomas: Single-institution study and a systematic review with meta-analysis|url=https://pubmed.ncbi.nlm.nih.gov/27575681|journal=Neurologia I Neurochirurgia Polska|volume=50|issue=6|pages=439–448|doi=10.1016/j.pjnns.2016.08.003|issn=0028-3843|pmid=27575681}}</ref>PMID:27575681; <ref name=":50">{{Cite journal|last=Lee|first=Yohan|last2=Liu|first2=Jason|last3=Patel|first3=Shilpa|last4=Cloughesy|first4=Timothy|last5=Lai|first5=Albert|last6=Farooqi|first6=Haumith|last7=Seligson|first7=David|last8=Dong|first8=Jun|last9=Liau|first9=Linda|date=2010-07|title=Genomic landscape of meningiomas|url=https://pubmed.ncbi.nlm.nih.gov/20015288|journal=Brain Pathology (Zurich, Switzerland)|volume=20|issue=4|pages=751–762|doi=10.1111/j.1750-3639.2009.00356.x|issn=1750-3639|pmc=3167483|pmid=20015288}}</ref>PMID:20015288 <ref>{{Cite journal|last=Jansen|first=M.|last2=Mohapatra|first2=G.|last3=Betensky|first3=R. 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| + | |- | ||
| + | | | ||
| + | |Grade 2 atypical | ||
| + | |'''Gain:''' 1q, 9q, 12q, 15q, 17q, 20q<br> | ||
| + | '''Loss:''' 1p, 3p, 6q, 7p, 14/14q, 9p, 10, 11p, 18/18q, 19q, 22/loss 22q | ||
| + | |'''Loss:''' [[NF2]], [[CDKN2A]], [[PTEN]]<br> | ||
| + | '''Mutation:''' [[NF2]], [[CDKN2A]]/[[CDKN2C]], [[SMARCE1]], [[SMARCB1]], [[TERT]] | ||
| + | |Gain of 1q is assocociated with a shorter PFS; Loss of 1p, 9p and 10 appear with greater frequency as tumor grade increases. | ||
| + | |<ref name=":24" />PMID:23528542; <ref name=":49" />PMID:27575681; <ref name=":50" />PMID:20015288 <ref name=":50" />PMID:21988727; <ref name=":51" />PMID19918127; <ref name=":52" />PMID:25347344 <ref name=":53" />PMID:23334667; <ref name=":54" />PMID:25963524; <ref name=":55" />PMID:26826201 <ref name=":56" />PMID:28195122; <ref name=":57" />PMID:26323607; <ref name=":58" />PMID:11958368; <ref name=":59" />PMID:25965831; <ref name=":60" />PMID:24536048; <ref name=":61" />PMID:24722350 <ref name=":62" />PMID:12568317; <ref name=":63" />PMID:26771848; <ref name=":64" />PMID:27012381; <ref name=":65" />PMID:27480481; <ref name=":66" />PMID:27624470; <ref name=":67" />PMID:27458586; <ref name=":68" />PMID:17225936 | ||
| + | |- | ||
| + | | | ||
| + | |Grade 3 anaplastic | ||
| + | |'''Gain:''' 1q, 9q, 12q, 15q, 17q23, 20q <br> | ||
| + | '''Loss:''' 1p, 3p, 6q, 7p, 14/14q, 9p, 10, 11p,18/18q,19q,22/loss 22q | ||
| + | |'''Loss:''' [[NF2]], [[CDKN2A]], [[PTEN]]<br> | ||
| + | '''Mutation:''' [[NF2]], [[CDKN2A]]/[[CDKN2C]], [[TERT]]<br> | ||
| + | '''Amplification:''' RPS6K in higher grades, 17q23 | ||
| + | |Loss of 9p and amplification or gain of 17q23 are more frequent than other abnormalities. Gain of 1q is assocociated with a shorter PFS; Loss of 1p, 9p and 10 appear with greater frequency as tumor grade increases. | ||
| + | |<ref name=":24" />PMID:23528542; <ref name=":49" />PMID:27575681; <ref name=":50" />PMID:20015288 <ref name=":50" />PMID:21988727; <ref name=":51" />PMID19918127; <ref name=":52" />PMID:25347344 <ref name=":53" />PMID:23334667; <ref name=":54" />PMID:25963524; <ref name=":55" />PMID:26826201 <ref name=":56" />PMID:28195122; <ref name=":57" />PMID:26323607; <ref name=":58" />PMID:11958368; <ref name=":59" />PMID:25965831; <ref name=":60" />PMID:24536048; <ref name=":61" />PMID:24722350 <ref name=":62" />PMID:12568317; <ref name=":63" />PMID:26771848; <ref name=":64" />PMID:27012381; <ref name=":65" />PMID:27480481; <ref name=":66" />PMID:27624470; <ref name=":67" />PMID:27458586; <ref name=":68" />PMID:17225936 | ||
| + | |- | ||
| + | |'''EPENDYMOMA'''<br> | ||
| + | (in order of increasing WHO grade) | ||
| + | | | ||
| + | |'''DNA-based methylation classifies''' tumors across anatomical sites --- intracranial (posterior fossa or supratentorial) or spinal --- and across tumor grades and age groups | ||
| + | |'''Fusion:''' [[YAP1]] fusions (supratentorial tumors)<br> | ||
| + | '''Mutation:''' [[NF2]] (spinal tumors)<br> | ||
| + | '''Loss:''' [[CDKN2A]] | ||
| + | |Intracranial (in children, 90%) or spinal tumors; Histological distinction between WHO grade II and III is not reliable; Prognostic differences among tumors suggested on the basis of methylation analysis | ||
| + | |WHO CNS Tumors (2016)<br> | ||
| + | <ref name=":16" />PMID:25965575; <ref name=":17" />PMID:21627842; <ref name=":18" />PMID:24939246; <ref name=":19" />PMID:22516549 | ||
| + | |- | ||
| + | | | ||
| + | |Classic ependymoma (no WHO grade assigned) | ||
| + | |'''Gain:''' 1q, 5, 7, 9, 11, 18, 20<br> | ||
| + | '''Loss:''' 1p, 3, -6/6q, 9p, 13q, 17, 22 | ||
| + | |'''Loss:''' [[CDKN2A]]/[[CDKN2B]] (rare); [[NF2]]<br> | ||
| + | '''Mutation:''' [[NF2]] (esp. in spinal tumors) | ||
| + | |Usually intracranial, spinal tumors (myxopapillary) are rare; 80% of pediatric tumors develop in posterior fossa (PF); Supratentorial tumors preferentially show monosomy 9; 1q gain is unfavorable prognostic indicator in PF tumors; spinal tumors associated with NF2 mutation (germline) | ||
| + | |<ref name=":16" />PMID:25965575; <ref name=":21" />PMID:22338015; <ref name=":22" />PMID:28371821 | ||
| + | |- | ||
| + | | | ||
| + | |Subependymoma, WHO grade I <br> | ||
| + | (intracranial or spinal) | ||
| + | |Typically '''balanced genomes'''<br> | ||
| + | '''Loss:''' -6/6q in spinal tumors | ||
| + | |No diagnostic mutations | ||
| + | |Favorable prognosis | ||
| + | |WHO CNS Tumors (2016)<br> | ||
| + | <ref name=":20" />PMID:21959044; <ref name=":23" />PMID:21840481 | ||
| + | |- | ||
| + | | | ||
| + | |Myxopapillary ependymoma, WHO grade I (spinal) | ||
| + | |'''Aneuploidy:''' multiple chromosomes lost and gained | ||
| + | |'''Mutation:''' [[NF2]] (including germline) in spinal tumors | ||
| + | |More common in adults | ||
| + | |<ref name=":16" />PMID:25965575; <ref name=":24" />PMCID:3991130; <ref name=":25" />PMID:20425037 <ref name=":26" />PMID:25957288; <ref name=":19" />PMID:22516549 | ||
| + | |- | ||
| + | | | ||
| + | |Ependymoma, RELA fusion-positive, WHO grade II or III<br> | ||
| + | (intracranial) | ||
| + | |'''Gain:''' 1q<br> | ||
| + | '''Aneuploidy:''' multiple chromosomes lost and gained<br> | ||
| + | '''Chromothripsis:''' chromosome 11 (70% of supratentorial tumors) | ||
| + | |'''Fusion:''' [[C11ORF95]]-[[RELA]] (supratentorial tumors)<br> | ||
| + | '''Loss:''' [[CDKN2A]]/[[CDKN2B]] (may help distinguish from other supratentorial ependymomas) | ||
| + | |Unfavorable prognosis | ||
| + | |<ref name=":16" />PMID:25965575; <ref name=":27" />PMID:24553141; <ref name=":22" />PMID:28371821 | ||
| + | |- | ||
| + | | | ||
| + | |Anaplastic ependymoma (no WHO grade assigned; intracranial or spinal) | ||
| + | |'''Epigenetic studies''' suggest range of abnormalities: balanced or unbalanced genomes | ||
| + | |'''Mutation:''' [[NF2]] (including germline) in spinal tumors<br> | ||
| + | '''Fusion:''' [[RELA]] fusions, [[YAP1]] fusions can correspond to anaplastic histology | ||
| + | |Mostly intracranial tumors, rarely in spinal cord | ||
| + | |<ref name=":16" />PMID: 25965575; <ref>{{Cite journal|last=Wu|first=Jing|last2=Armstrong|first2=Terri S.|last3=Gilbert|first3=Mark R.|date=2016-07|title=Biology and management of ependymomas|url=https://pubmed.ncbi.nlm.nih.gov/27022130|journal=Neuro-Oncology|volume=18|issue=7|pages=902–913|doi=10.1093/neuonc/now016|issn=1523-5866|pmc=4896548|pmid=27022130}}</ref>PMID:27022130 | ||
| + | |} | ||
| + | |||
| + | ==Reference== | ||
| + | 1. Neill SG, Hauenstein J, Li MM, Liu YJ, Luo M, Saxe DF, Ligon AH. (2020-05). Copy number assessment in the genomic analysis of CNS neoplasia: An evidence-based review from the cancer genomics consortium (CGC) working group on primary CNS tumors. Cancer Genetics. 243: 19–47. PMID 32203924. | ||
| + | <references /> | ||
Latest revision as of 17:05, 20 April 2021
Recurrent Genomic Alterations in Pediatric and Adult Central Nervous System Tumors Detected by Chromosomal Microarray
Table 1: Pediatric CNS Tumors. CGC CNS Workgroup 2015-2018. Table derived from Neill et al., 2020 [PMID: 32203924] with permission from Cancer Genetics.
| TUMOR | SUBTYPES | BROAD ABERRATIONS (>10Mb) | FOCAL ABERRATIONS (<10Mb) | CLINICAL FEATURES | REFERENCES |
|---|---|---|---|---|---|
| GLIOMAS | WHO CNS Tumors (2016) | ||||
| Low grade glioma, WHO grade I | Pilocytic astrocytoma/pilomyxoid astrocytoma | Some tumors show polysomy 7; other polysomies more common in adult PA | Fusions: KIAA1549-BRAF fusion (via 3'BRAF duplication), other BRAF partners reported; NTRK fusions (rare); FGFR1 fusions (rare) Mutations: BRAF V600E (particularly extra-cerebellar tumors); FGFR1 (midline PA); NF1 (esp. germline), other MAPK pathway mutations |
Classic PA are cerebellar (most commonly associated with BRAF duplication); PA in patients with germline NF1 alterations often develop as optic gliomas;Surgical resection can be curative; PMA generally more aggressive than PA; BRAF fusions and BRAF mutations generally are mutually exclusive | [1]PMID:19016743; [2]PMCID:2761618; [3]PMID:18716556 [4]PMID:25461780 [5]PMID:25664944; [6]PMID:26378811 [7]PMCID:3429698; [8]PMID:23817572; [9]PMID:23583981 [10]PMID:18974108; [11]PMID:23278243; [12]PMID:21274720 |
| Angiocentric glioma | Aberrations involving 6q24-q25 | Fusions: MYB-QKI rearrangement/deletion (classic histology) Rearrangement: MYB alone (atypical histology) |
Generally indolent tumors; surgical resection can be curative | [13]PMID:26829751; [14]PMID:23633565; [15]PMID:26778052 [9]PMID:23583981 | |
| Ganglioglioma | Only 30% are abnormal by karyotype Gain: polysomy 7 |
Mutations: BRAF V600E in 20-60% of cases (can be concurrent with CDKN2A homozygous deletion) |
Generally indolent tumors for which surgical resection can be curative | [4]PMID:25461780; [9]PMID:23583981; [16]PMID:11996800 [17]PMID:23609006; [18]PMID:29880043 | |
| Low grade glioma, WHO grade II | Diffuse astrocytoma | No diagnostic aberrations | Rearrangement: MYBL1 truncating rearrangements and tandem duplication, FGFR1 rearrangements Mutation: FGFR1 |
Anaplastic features associated with decreased progression free survival | [5]PMID:25664944; [14]PMID:23633565; [19]PMID:26061751 [20]PMID:26824661; [21]PMID:26004297; [4]PMID:25461780 [9]PMID:23583981 |
| Pleomorphic xanthoastrocytoma (PXA) | Polysomy 3, polysomy 7 observed Loss: monosomy 9 / 9p deletion |
Mutations: BRAF V600E in ~60%; TP53 (5%) |
[4]PMID:25461780; [9]PMID:23583981; [22]PMID:16909113; [23]PMID:12484572 | ||
| Anaplastic astrocytoma, WHO grade III | IDH-mutant or IDH-wild type | Gain: 1q, 7/7q, 8q, 10p Loss: 6q, 9p, 10q, -11/11p, 12q, 13q, 14q, 17p, 19q, -22/22q |
IDH-wild type astrocytomas can be more clinically aggressive than those that are IDH-mutant | [24]PMCID:1891902; [21]PMID:26004297; [4]PMID:25461780; [25]PMID:24140581; [26]PMCID:5323185; [27]PMID:27230974 [28]PMID:27196377; [19]PMID:26061751; [29]PMID:25962792; [30]PMID:29687258 | |
| Other | Anaplastic PXA, WHO grade III / Ganglioglioma, WHO Grade III | Loss: monosomy 9 / 9p deletion, but no diagnostic findings | Mutation: BRAF V600E less common here than in PXA, grade II |
CDKN2A/CDKN2B loss may correlate with anaplastic histology | WHO CNS Tumors (2016) |
| Glioblastoma, WHO grade IV | IDH-mutant | Gain: 1q, 2q, 3q, 7, 16p, 17q, 21q Loss: 6q, 8q, 9p, 9q, 10q, 13q, 17p, 22q |
Loss: PTEN, RB1, TP53, CDKN2A/CDKN2B/CDKN2C
Fusions: FGFR-TACC; NTRK fusions |
Overall poor prognosis | [33]PMID:25752754; [34]PMID:25727226; [35]PMID:26328271; [36]PMID:22837387; [37]PMID:25754088; [4]PMID:25461780; [24]PMCID:1891902; [38]PMID:23417712; [26]PMCID:5323185; [30]PMID:29687258; [39]PMID:20479398; [40]PMID:24959384 |
| Diffuse midline glioma, H3 K27M mutant | Gain: 1q, 2, 7, 8 Loss: 10q |
Three molecular subgroups: MYCN subgroup: no mutations but chromothripsis leading to amp of MYCN and ID2 |
Overall poor prognosis regardless of subgroup | [41]PMCID:3280796; [42]PMID:24705254; [43]PMID:24705252 [44]PMID:27048880; [45]PMID:26175967; [46]PMID:24705251; [47]PMID:28966033 | |
| EPENDYMOMA (in order of increasing WHO grade) |
DNA-based methylation classifies tumors across anatomical sites (posterior fossa, supratentorial, spinal), grades and age groups | Fusion: YAP1 fusions (supratentorial tumors) |
Intracranial (in children, 90%) or spinal tumors; Histological distinction between WHO grade II and III is of questionable relevance; Prognostic differences among tumors suggested on the basis of methylation analysis | WHO CNS Tumors (2016) [48]PMID:25965575; [49]PMID:21627842; [50]PMID:24939246; [51]PMID:22516549 | |
| Classic ependymoma (no WHO grade assigned) | Gain: 1q, 5, 7, 9, 11, 18, 20 Loss: 1p, 3, -6/6q, 9p, 13q, 17, 22 |
Usually intracranial, spinal tumors (myxopapillary) are rare; 80% of pediatric tumors develop in posterior fossa (PF); Supratentorial tumors preferentially show monosomy 9; 1q gain is unfavorable prognostic indicator in PF tumors; spinal tumors associated with NF2 (germline); children have worse outcomes than adults | [48]PMID:25965575; [52]PMID:22338015; [53]PMID:28371821 | ||
| Subependymoma, WHO grade I | Typically balanced genomes Loss: -6/6q in spinal tumors |
No diagnostic mutations | Favorable prognosis | WHO CNS Tumors (2016) | |
| Myxopapillary ependymoma, WHO grade I | Aneuploidy: multiple chromosomes lost and gained | Mutation: NF2 (including germline) in spinal tumors | Less common but more aggressive in children | [48]PMID:25965575; [56]PMCID:3991130; [57]PMID:20425037; [58]PMID:25957288; [51]PMID:22516549 | |
| Ependymoma, RELA fusion-positive, WHO grade II or III | Gain: 1q Aneuploidy: multiple chromosomes lost and gained |
Fusion: C11ORF95-RELA (supratentorial tumors) Loss: CDKN2A/CDKN2B (may help distinguish from other supratentorial ependymomas) |
Unfavorable prognosis; occur in infants or children | [48]PMID:25965575; [59]PMID:24553141; [53]PMID:28371821 | |
| Anaplastic ependymoma (no WHO grade assigned) | Epigenetic studies suggest range of abnormalities: balanced or unbalanced genomes | Mutation: NF2 (including germline) in spinal tumors Fusion: RELA fusions, YAP1 fusions can correspond to anaplastic histology |
Mostly intracranial tumors, rarely in spinal cord; YAP1 fusion tumors can occur in infants | [48]PMID: 25965575 | |
| EMBRYONAL TUMORS | WHO CNS Tumors (2016) | ||||
| Medulloblastoma | WNT-activated | Loss: monosomy 6/6q- as sole finding in 85% | Mutation: CTNNB1, DDX3X, TP53, SMARCA4, KMT2D, APC (germline mutations in Turcot syndrome) | Common in children > 3 years of age; typically show classic histology, rarely metastasize; overall favorable prognosis | [60]PMID:22832581, [61]PMID:24493713; [62]PMID:22134537 [63]PMID:24894640; [64]PMID:16258095; [65]PMID:22358457; [66]PMID:25043047 [67]PMID:22820256; [68]PMID:26976201; [69]PMID:20823417 [70]PMID:22265402; [71]PMCID:3889646; [72]PMID:16567768 [73]PMID:20940197 |
| SHH-activated | Gain: 3q Loss: 9q, 10q, 17p |
Mutation: TP53 wild-type tumors: PTCH1 (germline mutations in Gorlin syndrome), SMO, SUFU (can be germline), TERT promoter |
Common in infants, rare in children, most common type of medulloblastoma in adults; Desmoplastic (or nodular) histology common; TP53 wild-type usually correlate with extensive nodularity or desmoplastic histology; TP53-mutant tumors correlate with metastatic disease | [74]PMID:24651015; [75]PMID:21681522; [60]PMID:22832581 [61]PMID:24493713; [76]PMID:24077351; [62]PMID:22134537; [65]PMID:22358457 [66]PMID:25043047; [67]PMID:22820256; [68]PMID:26976201 [68]PMID:20823417; [70]PMID:22265402; [71]PMCID:3889646 [72]PMID:16567768; [73]PMID:20940197 | |
| Group3 | Gain: 1q, 7, 18q Loss: 5q, 8, 10q, 11p, 16q |
Mutation/Amplification: MYC (mainly in infants), OTX2, CDK6, SMARC4A, CTDNEP1, LRP1B, KMT2D Fusions: PVT1-MYC, PVT1-NDRG1; GFI1/GFI1B structural variants |
Usually classic histology, ~ 50% are metastatic at time of diagnosis, Not generally observed in adults | [60]PMID:22832581, [66]PMID:25043047; [61]PMID:24493713 [62]PMID:22134537; [65]PMID:22358457; [67]PMID:22820256; [68]PMID:26976201; [68]PMID:20823417 [70]PMID:22265402; [71]PMCID:3889646; [72]PMID:16567768 [73]PMID:20940197 | |
| Group4 | Gain: 7, 18q Loss: X, 8, 11p |
Mutation: TP53, KDM6A, KMT2C Amplification: MYCN, CDK4, CDK6, OTX2 |
Rarely seen in infants; usually classic histology | [60]PMID:22832581; [66]PMID:25043047; [61]PMID:24493713; [62]PMID:22134537; [65]PMID:22358457; [67]PMID:22820256; [68]PMID:26976201; [68]PMID:20823417 [70]PMID:22265402; [71]PMCID:3889646; [72]PMID:16567768 [73]PMID:20940197 | |
| Atypical teratoid/rhabdoid tumor (AT/RT) | Loss: 22/22q, though a subset of AT/RT-like tumors retain 22q | Classic AT/RT: SMARCB1 mutation/deletion/exonic duplication in 98% of tumors AT/RT-like tumors: SMARCB1 can be retained (with SMARCA4 mutations) |
Most cases occur before 3 yrs of age TYR subclass: mostly infratentorial |
||
| Embryonal tumor with multilayered rosettes, C19MC-altered | ETMR (incl. ETANTR): occasionally polysomy 2 | ETANTR: miRNA cluster C19MC amplification | Occurs mainly in children < 4 yrs old | WHO CNS Tumors (2016) [77]PMID:24839957; [78]PMID:24470553 [79]PMID:24337497; [80]PMID:22324795 [81]PMID:20407781, [82]PMID:19057917 | |
| Embryonal tumor, other | CNS NB-FOXR2 group: 1q gain, 16q loss, polysomy 8 CNS EFT-CIC group: polysomy 8 |
CNS NB-FOXR2 group: JMJD1C fusions, FOXR2 fusion or deletion CNS EFT-CIC group: NUTM1 rearrangement/fusion, CIC rearrangement |
Most common in children, but may also occur in adolescents and adults | WHO CNS Tumors (2016) | |
| CHOROID PLEXUS TUMORS (CPT) | Choroid plexus papilloma(CPP, WHO grade I) and atypical choroid plexus papilloma (WHO grade II) | Hyperdiploidy Loss: rare, no recurrent losses |
No diagnostic mutations/events | CPP and aCPP likely belong to same molecularly defined entity; CPP is a diagnostic feature of Aircardi syndrome | WHO CNS Tumors (2016) [86]PMID:23172371; [87]PMID:25575132; [88]PMID:25336695 [89]PMID:11891207 |
| Choroid plexus carcinoma (CPC, WHO grade III) | Aneuploidy (including both hypo- and hyperdiploidy types of CPC); copy neutral LOH is frequent, particularly involving chromosome 17 Gain: 1, 7, 12, 20 in > 80% of hyperdiploid CPCs |
Mutation: TP53 in > 50% Amplification: PDGFRB |
80% occur in children; associated with Li-Fraumeni syndrome; Lack of SMARCB1/SMARCA4 aberrations can be used to distinguish CPC from AT/RT | [90]PMID:24478045; [91]PMID:21990040; [87]PMID:25575132; [92]PMID:18157090; [88]PMID:25336695 |
Table 2: Adult CNS Tumors. CGC CNS Workgroup 2015-2018. Table derived from Neill et al., 2020 [PMID: 32203924] with permission from Cancer Genetics.
| TUMOR | SUBTYPES | BROAD ABERRATIONS (>10Mb) | FOCAL ABERRATIONS (<10Mb) | CLINICAL FEATURES | REFERENCES |
|---|---|---|---|---|---|
| GLIOMAS | |||||
| Low grade gliomas, WHO grade I-II | Pilocytic astrocytoma | Gain: 5, 7, 6, 11 Loss: 1, 2, 3, 13, 14, 16, 17, 19 |
Fusion: KIAA1549-BRAF fusion (via 3'BRAF duplication), other BRAF partners reported; NTRK fusions (rare) Mutation: FGFR1 |
Aneuploidy is more predominant in adult PA; Infratentorial tumors are more likely to have BRAF fusions/dup and be wildtype for BRAF mutations; Extra-cerebellar tumors are more likely to be BRAF V600E+, but negative for fusion; Surgical resection can be curative | [93]PMID: 24470550; [6]PMID:26378811; [5]PMID: 25664944; [94]PMID:26992069 |
| Pleomorphic xanthoastrocytoma (PXA) | Gain: 7, 2, 5, 21, 20, 12, 15 Loss: monosomy 9 / 9p deletion most common, 22, 14, 13, 10 |
Loss: homozygous loss CDKN2A/CDKN2B Mutation: BRAF V600E |
Adults and pediatric tumors show similar CNVs; CDKN2A/CDKN2B loss may correlate with anaplastic histology | [95]PMID:23442159; [96]PMID:28181325 | |
| Ganglioglioma | Gain: polysomy 5, polysomy 7, 10p Loss: 1p loss, monosomy (with focal CDKN2A loss) |
Mutation: BRAF V600E, TSC1, TSC2, FGFR1, FGFR2, KRAS | Generally indolent tumors; surgical resection can be curative | [95]PMID:23442159; [97]PMID:25764012; [18]PMID:29880043 | |
| Angiocentric glioma | Loss: 6q24-q25 | Fusion: MYB-QKI rearrangement/deletion (classic histology) Rearrangement: MYB alone (atypical histology) |
Generally indolent tumors; surgical resection can be curative | [13]PMID:26829751 | |
| Dysembryoplastic neuroepithelial tumor (DNET) | No specific changes | Mutation: intragenic duplication or mutation FGFR1; BRAF V600E | Rare in adults; Benign with excellent prognosis even with subtotal resection | [98]PMID:26920151; [95]PMID:23442159; [99]PMID:21937911 | |
| Rosette forming glioneuronal tumor | Gain:1q , 7, 9, 16 Loss: 1p |
Fusion: KIAA1549-BRAF fusion (via 3'BRAF duplication) |
Generally indolent tumors; surgical resection can be curative | [100]PMID:27893178; [101]PMID:26371886 | |
| Infiltrating Gliomas | Diffuse astrocytoma/anaplastic Astrocytoma, WHO grade II/III, IDH mutant | Gain: 4q, 7q, 8q24, 12q Loss: 9p, 19q (without 1p) |
Gain: MYC |
Better prognosis than IDH wildtype astrocytoma; Progression to grade IV will often involves loss of 10q, gain of CDK4, CDK6, and cyclin E2, and an increase in copy number alterations. | [20]PMID:26824661; [102]PMID:26061753; [103]PMID:25263767 [104]PMID:26061754; [105]PMID:28535583; [106]PMID:26091668 [107]PMID: 25701198; [108]PMID:26865861; [30]PMID:29687258 |
| Diffuse astrocytoma/anaplastic astrocytoma, WHO grade II/III, IDH wild-type | Gain: 7, 19 |
Loss: homozygous CDKN2A/CDKN2B |
Poor prognosis with similar abnormalities to glioblastoma | [104]PMID:26061754; [20]PMID:26824661; [105]PMID:28535583 [106]PMID:26091668; [109]PMID:26810070 | |
| Oligodendroglioma/anaplastic oligodendroglioma, WHO grade II/III, IDH mutant | Rearrangement: der(1;19)(q10;p10) leads to 1p/19q co-deletion Loss: 1p/19q, 9p, 14q, less frequent 4, 18q |
Gain: MYC Loss: MAX (14q), FBXW7, CDKN2A/CDKN2B |
Activation of MYC pathway is often seen with loss of 9p (CDKN2A/B), and 14q (MAX gene) and is reported to have a worse prognosis | [110]PMID:27090007; [102]PMID:26061753; [103]PMID:25263767 [104]PMID:26061754; [111]PMID:24335697; [5]PMID:25664944; [112]PMID:26941959; [20]PMID:26824661 [19]PMID:26061751 | |
| Glioblastoma , grade IV, IDH mutant | Gain: 1/1q, 6p Loss: 3p, 10, 13, 14, 15, 22 (3, 4q, 19q, 16p, 21q, 5p seen in age <40) |
Gain or Amplification: CDK4, CDK6, cyclin E2 (CCNE2) Loss: PTEN |
About 10% of glioblastomas; correspond closely to secondary glioblastoma with history of prior glioma. These cases often involve loss of 10q , gain of CDK4, CDK6, cyclin E2, and increase in copy number alterations. | [104]PMID:26061754; [37]PMID:25754088; [105]PMID:28535583 [113]PMID:25931051; [106]PMID:26091668; [4]PMID:25461780; [114]PMID:27157931; [34]PMID:25727226; [115]PMID:26323991 [19]PMID:26061751; [30]PMID:29687258 | |
| Glioblastoma , grade IV, IDH wildtype | Loss: 4, 9p, 10, 13, 14, 15, 22 , (3, 4q, 19q, 16p, 21q, 5p loss in age <40) Gain: 7, 19, 20 (1q, 12p, 11q, 9q, 4, 10p gain in age <40) |
Loss: homozygous CDKN2A/CDKN2B, PTEN, RB1 Mutation: TERT, EGFR, PTEN, NF1, RB1, PIK3CA or PIK3R1, TP53 |
Overall poor prognosis. Gain of 19q, amplification of EGFR, and homozygous loss of CDKN2A are seen primarily in patients over age 40. Co-gain of 19 and 20 may be associated with longer survival. | [104]PMID:26061754; [37]PMID:25754088; [105]PMID:28535583 [113]PMID:25931051; [106]PMID:26091668; [4]PMID:25461780; [114]PMID:27157931; [34]PMID:25727226; [19]PMID:26061751 | |
| MENINGIOMA | |||||
| Grade 1 | No copy number changes in 44% Gain: multiple polysomies, 5 |
Loss: NF2, CDKN2A, PTEN |
Array findings characteristic of higher grade tumors when histology supports lower grade may suggest increased likelihood of recurrence. Polysomy, particularly involving chromosome 5, are seen in angiomatous meningiomas. LOH 1p and/or LOH 1p/14q correlated with anaplastic transformation. | [56]PMID:23528542; [116]PMID:27575681; [117]PMID:20015288 [118]PMID:21988727; [119]PMID19918127; [120]PMID:25347344 [121]PMID:23334667; [122]PMID:25963524; [123]PMID:26826201 [124]PMID:28195122; [125]PMID:26323607;
[126]PMID:11958368; [127]PMID:25965831; [128]PMID:24536048; [129]PMID:24722350 [130]PMID:12568317; [131]PMID:26771848; [132]PMID:27012381; [133]PMID:27480481; [134]PMID:27624470; [135]PMID:27458586; [136]PMID:17225936 | |
| Grade 2 atypical | Gain: 1q, 9q, 12q, 15q, 17q, 20q Loss: 1p, 3p, 6q, 7p, 14/14q, 9p, 10, 11p, 18/18q, 19q, 22/loss 22q |
Loss: NF2, CDKN2A, PTEN |
Gain of 1q is assocociated with a shorter PFS; Loss of 1p, 9p and 10 appear with greater frequency as tumor grade increases. | [56]PMID:23528542; [116]PMID:27575681; [117]PMID:20015288 [117]PMID:21988727; [119]PMID19918127; [120]PMID:25347344 [121]PMID:23334667; [122]PMID:25963524; [123]PMID:26826201 [124]PMID:28195122; [125]PMID:26323607; [126]PMID:11958368; [127]PMID:25965831; [128]PMID:24536048; [129]PMID:24722350 [130]PMID:12568317; [131]PMID:26771848; [132]PMID:27012381; [133]PMID:27480481; [134]PMID:27624470; [135]PMID:27458586; [136]PMID:17225936 | |
| Grade 3 anaplastic | Gain: 1q, 9q, 12q, 15q, 17q23, 20q Loss: 1p, 3p, 6q, 7p, 14/14q, 9p, 10, 11p,18/18q,19q,22/loss 22q |
Loss: NF2, CDKN2A, PTEN Mutation: NF2, CDKN2A/CDKN2C, TERT |
Loss of 9p and amplification or gain of 17q23 are more frequent than other abnormalities. Gain of 1q is assocociated with a shorter PFS; Loss of 1p, 9p and 10 appear with greater frequency as tumor grade increases. | [56]PMID:23528542; [116]PMID:27575681; [117]PMID:20015288 [117]PMID:21988727; [119]PMID19918127; [120]PMID:25347344 [121]PMID:23334667; [122]PMID:25963524; [123]PMID:26826201 [124]PMID:28195122; [125]PMID:26323607; [126]PMID:11958368; [127]PMID:25965831; [128]PMID:24536048; [129]PMID:24722350 [130]PMID:12568317; [131]PMID:26771848; [132]PMID:27012381; [133]PMID:27480481; [134]PMID:27624470; [135]PMID:27458586; [136]PMID:17225936 | |
| EPENDYMOMA (in order of increasing WHO grade) |
DNA-based methylation classifies tumors across anatomical sites --- intracranial (posterior fossa or supratentorial) or spinal --- and across tumor grades and age groups | Fusion: YAP1 fusions (supratentorial tumors) |
Intracranial (in children, 90%) or spinal tumors; Histological distinction between WHO grade II and III is not reliable; Prognostic differences among tumors suggested on the basis of methylation analysis | WHO CNS Tumors (2016) [48]PMID:25965575; [49]PMID:21627842; [50]PMID:24939246; [51]PMID:22516549 | |
| Classic ependymoma (no WHO grade assigned) | Gain: 1q, 5, 7, 9, 11, 18, 20 Loss: 1p, 3, -6/6q, 9p, 13q, 17, 22 |
Loss: CDKN2A/CDKN2B (rare); NF2 Mutation: NF2 (esp. in spinal tumors) |
Usually intracranial, spinal tumors (myxopapillary) are rare; 80% of pediatric tumors develop in posterior fossa (PF); Supratentorial tumors preferentially show monosomy 9; 1q gain is unfavorable prognostic indicator in PF tumors; spinal tumors associated with NF2 mutation (germline) | [48]PMID:25965575; [52]PMID:22338015; [53]PMID:28371821 | |
| Subependymoma, WHO grade I (intracranial or spinal) |
Typically balanced genomes Loss: -6/6q in spinal tumors |
No diagnostic mutations | Favorable prognosis | WHO CNS Tumors (2016) | |
| Myxopapillary ependymoma, WHO grade I (spinal) | Aneuploidy: multiple chromosomes lost and gained | Mutation: NF2 (including germline) in spinal tumors | More common in adults | [48]PMID:25965575; [56]PMCID:3991130; [57]PMID:20425037 [58]PMID:25957288; [51]PMID:22516549 | |
| Ependymoma, RELA fusion-positive, WHO grade II or III (intracranial) |
Gain: 1q Aneuploidy: multiple chromosomes lost and gained |
Fusion: C11ORF95-RELA (supratentorial tumors) Loss: CDKN2A/CDKN2B (may help distinguish from other supratentorial ependymomas) |
Unfavorable prognosis | [48]PMID:25965575; [59]PMID:24553141; [53]PMID:28371821 | |
| Anaplastic ependymoma (no WHO grade assigned; intracranial or spinal) | Epigenetic studies suggest range of abnormalities: balanced or unbalanced genomes | Mutation: NF2 (including germline) in spinal tumors Fusion: RELA fusions, YAP1 fusions can correspond to anaplastic histology |
Mostly intracranial tumors, rarely in spinal cord | [48]PMID: 25965575; [137]PMID:27022130 |
Reference
1. Neill SG, Hauenstein J, Li MM, Liu YJ, Luo M, Saxe DF, Ligon AH. (2020-05). Copy number assessment in the genomic analysis of CNS neoplasia: An evidence-based review from the cancer genomics consortium (CGC) working group on primary CNS tumors. Cancer Genetics. 243: 19–47. PMID 32203924.
- ↑ Sievert, Angela J.; et al. (2009-07). "Duplication of 7q34 in pediatric low-grade astrocytomas detected by high-density single-nucleotide polymorphism-based genotype arrays results in a novel BRAF fusion gene". Brain Pathology (Zurich, Switzerland). 19 (3): 449–458. doi:10.1111/j.1750-3639.2008.00225.x. ISSN 1750-3639. PMC 2850204. PMID 19016743. Check date values in:
|date=(help) - ↑ Jones, David T. W.; et al. (2006-11). "Genomic Analysis of Pilocytic Astrocytomas at 0.97 Mb Resolution Shows an Increasing Tendency Toward Chromosomal Copy Number Change With Age". Journal of neuropathology and experimental neurology. 65 (11): 1049–1058. doi:10.1097/01.jnen.0000240465.33628.87. ISSN 0022-3069. PMC 2761618. PMID 17086101. Check date values in:
|date=(help) - ↑ Bar, Eli E.; et al. (2008-09). "Frequent gains at chromosome 7q34 involving BRAF in pilocytic astrocytoma". Journal of Neuropathology and Experimental Neurology. 67 (9): 878–887. doi:10.1097/NEN.0b013e3181845622. ISSN 0022-3069. PMID 18716556. Check date values in:
|date=(help) - ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Appin, Christina L.; et al. (2015-01). "Molecular pathways in gliomagenesis and their relevance to neuropathologic diagnosis". Advances in Anatomic Pathology. 22 (1): 50–58. doi:10.1097/PAP.0000000000000048. ISSN 1533-4031. PMID 25461780. Check date values in:
|date=(help) - ↑ 5.0 5.1 5.2 5.3 Venneti, Sriram; et al. (2015-03). "The evolving molecular genetics of low-grade glioma". Advances in Anatomic Pathology. 22 (2): 94–101. doi:10.1097/PAP.0000000000000049. ISSN 1533-4031. PMC 4667550. PMID 25664944. Check date values in:
|date=(help) - ↑ 6.0 6.1 Fontebasso, Adam M.; et al. (2015-10-13). "Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age". Oncotarget. 6 (31): 31844–31856. doi:10.18632/oncotarget.5571. ISSN 1949-2553. PMC 4741644. PMID 26378811.
- ↑ Rodriguez, Fausto J.; et al. (2012-9). "BRAF Duplications and MAPK Pathway Activation Are Frequent in Gliomas of the Optic Nerve Proper". Journal of neuropathology and experimental neurology. 71 (9): 789–794. doi:10.1097/NEN.0b013e3182656ef8. ISSN 0022-3069. PMC 3429698. PMID 22892521. Check date values in:
|date=(help) - ↑ Jones, David T. W.; et al. (2013-08). "Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma". Nature Genetics. 45 (8): 927–932. doi:10.1038/ng.2682. ISSN 1546-1718. PMC 3951336. PMID 23817572. Check date values in:
|date=(help) - ↑ 9.0 9.1 9.2 9.3 9.4 Zhang, Jinghui; et al. (2013-06). "Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas". Nature Genetics. 45 (6): 602–612. doi:10.1038/ng.2611. ISSN 1546-1718. PMC 3727232. PMID 23583981. Check date values in:
|date=(help) - ↑ Jones, David T. W.; et al. (2008-11-01). "Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas". Cancer Research. 68 (21): 8673–8677. doi:10.1158/0008-5472.CAN-08-2097. ISSN 1538-7445. PMC 2577184. PMID 18974108.
- ↑ Colin, C.; et al. (2013-10). "Outcome analysis of childhood pilocytic astrocytomas: a retrospective study of 148 cases at a single institution". Neuropathology and Applied Neurobiology. 39 (6): 693–705. doi:10.1111/nan.12013. ISSN 1365-2990. PMID 23278243. Check date values in:
|date=(help) - ↑ 12.0 12.1 Schindler, Genevieve; et al. (2011-03). "Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma". Acta Neuropathologica. 121 (3): 397–405. doi:10.1007/s00401-011-0802-6. ISSN 1432-0533. PMID 21274720. Check date values in:
|date=(help) - ↑ 13.0 13.1 Bandopadhayay, Pratiti; et al. (2016-03). "MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism". Nature Genetics. 48 (3): 273–282. doi:10.1038/ng.3500. ISSN 1546-1718. PMC 4767685. PMID 26829751. Check date values in:
|date=(help) - ↑ 14.0 14.1 Ramkissoon, Lori A.; et al. (2013-05-14). "Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1". Proceedings of the National Academy of Sciences of the United States of America. 110 (20): 8188–8193. doi:10.1073/pnas.1300252110. ISSN 1091-6490. PMC 3657784. PMID 23633565.
- ↑ Ampie, Leonel; et al. (2016-06). "Clinical attributes and surgical outcomes of angiocentric gliomas". Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia. 28: 117–122. doi:10.1016/j.jocn.2015.11.015. ISSN 1532-2653. PMID 26778052. Check date values in:
|date=(help) - ↑ Yin, Xiao Lu; et al. (2002-04-01). "Genome-wide survey for chromosomal imbalances in ganglioglioma using comparative genomic hybridization". Cancer Genetics and Cytogenetics. 134 (1): 71–76. doi:10.1016/s0165-4608(01)00611-2. ISSN 0165-4608. PMID 11996800.
- ↑ Dahiya, Sonika; et al. (2013-06). "BRAF(V600E) mutation is a negative prognosticator in pediatric ganglioglioma". Acta Neuropathologica. 125 (6): 901–910. doi:10.1007/s00401-013-1120-y. ISSN 1432-0533. PMID 23609006. Check date values in:
|date=(help) - ↑ 18.0 18.1 Pekmezci, Melike; et al. (2018-06-07). "The genetic landscape of ganglioglioma". Acta Neuropathologica Communications. 6 (1): 47. doi:10.1186/s40478-018-0551-z. ISSN 2051-5960. PMC 5992851. PMID 29880043.
- ↑ 19.0 19.1 19.2 19.3 19.4 Cancer Genome Atlas Research Network; et al. (2015-06-25). "Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas". The New England Journal of Medicine. 372 (26): 2481–2498. doi:10.1056/NEJMoa1402121. ISSN 1533-4406. PMC 4530011. PMID 26061751.
- ↑ 20.0 20.1 20.2 20.3 Ceccarelli, Michele; et al. (2016-01-28). "Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma". Cell. 164 (3): 550–563. doi:10.1016/j.cell.2015.12.028. ISSN 1097-4172. PMC 4754110. PMID 26824661.
- ↑ 21.0 21.1 Appin, Christina L.; et al. (2015-11). "Biomarker-driven diagnosis of diffuse gliomas". Molecular Aspects of Medicine. 45: 87–96. doi:10.1016/j.mam.2015.05.002. ISSN 1872-9452. PMID 26004297. Check date values in:
|date=(help) - ↑ Weber, R. G.; et al. (2007-02-15). "Frequent loss of chromosome 9, homozygous CDKN2A/p14(ARF)/CDKN2B deletion and low TSC1 mRNA expression in pleomorphic xanthoastrocytomas". Oncogene. 26 (7): 1088–1097. doi:10.1038/sj.onc.1209851. ISSN 0950-9232. PMID 16909113.
- ↑ Kaulich, Kerstin; et al. (2002-12). "Genetic alterations commonly found in diffusely infiltrating cerebral gliomas are rare or absent in pleomorphic xanthoastrocytomas". Journal of Neuropathology and Experimental Neurology. 61 (12): 1092–1099. doi:10.1093/jnen/61.12.1092. ISSN 0022-3069. PMID 12484572. Check date values in:
|date=(help) - ↑ 24.0 24.1 Rickert, Christian H.; et al. (2001-4). "Pediatric High-Grade Astrocytomas Show Chromosomal Imbalances Distinct from Adult Cases". The American Journal of Pathology. 158 (4): 1525–1532. doi:10.1016/S0002-9440(10)64103-X. ISSN 0002-9440. PMC 1891902. PMID 11290570. Check date values in:
|date=(help) - ↑ Killela, Patrick J.; et al. (2014-03-30). "The genetic landscape of anaplastic astrocytoma". Oncotarget. 5 (6): 1452–1457. doi:10.18632/oncotarget.1505. ISSN 1949-2553. PMC 4039223. PMID 24140581.
- ↑ 26.0 26.1 Koschmann, Carl; et al. (2016-08-25). "Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma". Oncotarget. 7 (40): 65696–65706. doi:10.18632/oncotarget.11602. ISSN 1949-2553. PMC 5323185. PMID 27582545.
- ↑ Grimm, Sean A.; et al. (2016-07). "Anaplastic astrocytoma". CNS oncology. 5 (3): 145–157. doi:10.2217/cns-2016-0002. ISSN 2045-0915. PMC 6042632. PMID 27230974. Check date values in:
|date=(help) - ↑ Hattori, Natsuki; et al. (2016-08). "World Health Organization grade II-III astrocytomas consist of genetically distinct tumor lineages". Cancer Science. 107 (8): 1159–1164. doi:10.1111/cas.12969. ISSN 1349-7006. PMC 4982592. PMID 27196377. Check date values in:
|date=(help) - ↑ Reuss, David E.; et al. (2015-06). "IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO". Acta Neuropathologica. 129 (6): 867–873. doi:10.1007/s00401-015-1438-8. ISSN 1432-0533. PMC 4500039. PMID 25962792. Check date values in:
|date=(help) - ↑ 30.0 30.1 30.2 30.3 Shirahata, Mitsuaki; et al. (2018-07). "Novel, improved grading system(s) for IDH-mutant astrocytic gliomas". Acta Neuropathologica. 136 (1): 153–166. doi:10.1007/s00401-018-1849-4. ISSN 1432-0533. PMID 29687258. Check date values in:
|date=(help) - ↑ Ida, Cristiane M.; et al. (2015-09). "Pleomorphic Xanthoastrocytoma: Natural History and Long-Term Follow-Up". Brain Pathology (Zurich, Switzerland). 25 (5): 575–586. doi:10.1111/bpa.12217. ISSN 1750-3639. PMC 4400218. PMID 25318587. Check date values in:
|date=(help) - ↑ Schmidt, Yao; et al. (2013-01). "Anaplastic PXA in adults: case series with clinicopathologic and molecular features". Journal of Neuro-Oncology. 111 (1): 59–69. doi:10.1007/s11060-012-0991-4. ISSN 1573-7373. PMC 4617340. PMID 23096133. Check date values in:
|date=(help) - ↑ Korshunov, Andrey; et al. (2015-05). "Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers". Acta Neuropathologica. 129 (5): 669–678. doi:10.1007/s00401-015-1405-4. ISSN 1432-0533. PMID 25752754. Check date values in:
|date=(help) - ↑ 34.0 34.1 34.2 Karsy, Michael; et al. (2015-03). "A practical review of prognostic correlations of molecular biomarkers in glioblastoma". Neurosurgical Focus. 38 (3): E4. doi:10.3171/2015.1.FOCUS14755. ISSN 1092-0684. PMID 25727226. Check date values in:
|date=(help) - ↑ Furgason, John M.; et al. (2015). "Whole genome sequence analysis links chromothripsis to EGFR, MDM2, MDM4, and CDK4 amplification in glioblastoma". Oncoscience. 2 (7): 618–628. doi:10.18632/oncoscience.178. ISSN 2331-4737. PMC 4549359. PMID 26328271.
- ↑ Singh, Devendra; et al. (2012-09-07). "Transforming fusions of FGFR and TACC genes in human glioblastoma". Science (New York, N.Y.). 337 (6099): 1231–1235. doi:10.1126/science.1220834. ISSN 1095-9203. PMC 3677224. PMID 22837387.
- ↑ 37.0 37.1 37.2 Ramkissoon, Shakti H.; et al. (2015-10). "Clinical implementation of integrated whole-genome copy number and mutation profiling for glioblastoma". Neuro-Oncology. 17 (10): 1344–1355. doi:10.1093/neuonc/nov015. ISSN 1523-5866. PMC 4578577. PMID 25754088. Check date values in:
|date=(help) - ↑ Fontebasso, Adam M.; et al. (2013-05). "Mutations in SETD2 and genes affecting histone H3K36 methylation target hemispheric high-grade gliomas". Acta Neuropathologica. 125 (5): 659–669. doi:10.1007/s00401-013-1095-8. ISSN 1432-0533. PMC 3631313. PMID 23417712. Check date values in:
|date=(help) - ↑ Paugh, Barbara S.; et al. (2010-06-20). "Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 28 (18): 3061–3068. doi:10.1200/JCO.2009.26.7252. ISSN 1527-7755. PMC 2903336. PMID 20479398.
- ↑ Giunti, Laura; et al. (2014). "Genome-wide copy number analysis in pediatric glioblastoma multiforme". American Journal of Cancer Research. 4 (3): 293–303. ISSN 2156-6976. PMC 4065410. PMID 24959384.
- ↑ Warren, Katherine E.; et al. (2012-3). "Genomic aberrations in pediatric diffuse intrinsic pontine gliomas". Neuro-Oncology. 14 (3): 326–332. doi:10.1093/neuonc/nor190. ISSN 1522-8517. PMC 3280796. PMID 22064882. Check date values in:
|date=(help) - ↑ Buczkowicz, Pawel; et al. (2014-05). "Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations". Nature Genetics. 46 (5): 451–456. doi:10.1038/ng.2936. ISSN 1546-1718. PMC 3997489. PMID 24705254. Check date values in:
|date=(help) - ↑ Taylor, Kathryn R.; et al. (2014-05). "Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma". Nature Genetics. 46 (5): 457–461. doi:10.1038/ng.2925. ISSN 1546-1718. PMC 4018681. PMID 24705252. Check date values in:
|date=(help) - ↑ Nikbakht, Hamid; et al. (2016-04-06). "Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma". Nature Communications. 7: 11185. doi:10.1038/ncomms11185. ISSN 2041-1723. PMC 4823825. PMID 27048880.
- ↑ Buczkowicz, Pawel; et al. (2015). "Pathology, Molecular Genetics, and Epigenetics of Diffuse Intrinsic Pontine Glioma". Frontiers in Oncology. 5: 147. doi:10.3389/fonc.2015.00147. ISSN 2234-943X. PMC 4485076. PMID 26175967.
- ↑ Wu, Gang; et al. (2014-05). "The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma". Nature Genetics. 46 (5): 444–450. doi:10.1038/ng.2938. ISSN 1546-1718. PMC 4056452. PMID 24705251. Check date values in:
|date=(help) - ↑ Mackay, Alan; et al. (2017-10-09). "Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma". Cancer Cell. 32 (4): 520–537.e5. doi:10.1016/j.ccell.2017.08.017. ISSN 1878-3686. PMC 5637314. PMID 28966033.
- ↑ 48.0 48.1 48.2 48.3 48.4 48.5 48.6 48.7 48.8 48.9 Pajtler, Kristian W.; et al. (2015-05-11). "Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups". Cancer Cell. 27 (5): 728–743. doi:10.1016/j.ccell.2015.04.002. ISSN 1878-3686. PMC 4712639. PMID 25965575.
- ↑ 49.0 49.1 Ellison, David W.; et al. (2011-05-31). "Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts". Journal of Negative Results in Biomedicine. 10: 7. doi:10.1186/1477-5751-10-7. ISSN 1477-5751. PMC 3117833. PMID 21627842.
- ↑ 50.0 50.1 Olsen, Thale Kristin; et al. (2014-08). "Genomic characterization of ependymomas reveals 6q loss as the most common aberration". Oncology Reports. 32 (2): 483–490. doi:10.3892/or.2014.3271. ISSN 1791-2431. PMC 4091878. PMID 24939246. Check date values in:
|date=(help) - ↑ 51.0 51.1 51.2 51.3 Yang, Isaac; et al. (2012-06). "Chromosomal anomalies and prognostic markers for intracranial and spinal ependymomas". Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia. 19 (6): 779–785. doi:10.1016/j.jocn.2011.11.004. ISSN 1532-2653. PMC 3615711. PMID 22516549. Check date values in:
|date=(help) - ↑ 52.0 52.1 Kilday, John-Paul; et al. (2012-04-01). "Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification: a prospective European clinical trial cohort analysis on behalf of the Children's Cancer Leukaemia Group (CCLG), Societe Francaise d'Oncologie Pediatrique (SFOP), and International Society for Pediatric Oncology (SIOP)". Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 18 (7): 2001–2011. doi:10.1158/1078-0432.CCR-11-2489. ISSN 1557-3265. PMID 22338015.
- ↑ 53.0 53.1 53.2 53.3 Gojo, Johannes; et al. (2017-09-01). "Telomerase activation in posterior fossa group A ependymomas is associated with dismal prognosis and chromosome 1q gain". Neuro-Oncology. 19 (9): 1183–1194. doi:10.1093/neuonc/nox027. ISSN 1523-5866. PMC 5570194. PMID 28371821.
- ↑ 54.0 54.1 Yao, Yuan; et al. (2011-10). "Molecular genetics of ependymoma". Chinese Journal of Cancer. 30 (10): 669–681. doi:10.5732/cjc.011.10129. ISSN 1000-467X. PMC 4012267. PMID 21959044. Check date values in:
|date=(help) - ↑ 55.0 55.1 Witt, Hendrik; et al. (2011-08-16). "Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma". Cancer Cell. 20 (2): 143–157. doi:10.1016/j.ccr.2011.07.007. ISSN 1878-3686. PMC 4154494. PMID 21840481.
- ↑ 56.0 56.1 56.2 56.3 56.4 Zadnik, Patricia L.; et al. (2013-5). "Spinal cord tumours: advances in genetics and their implications for treatment". Nature reviews. Neurology. 9 (5): 257–266. doi:10.1038/nrneurol.2013.48. ISSN 1759-4758. PMC 3991130. PMID 23528542. Check date values in:
|date=(help) - ↑ 57.0 57.1 Dubuc, Adrian M.; et al. (2010-05). "The genetics of pediatric brain tumors". Current Neurology and Neuroscience Reports. 10 (3): 215–223. doi:10.1007/s11910-010-0103-9. ISSN 1534-6293. PMID 20425037. Check date values in:
|date=(help) - ↑ 58.0 58.1 Mack, Stephen C.; et al. (2015-08-15). "Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype". Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 21 (16): 3750–3758. doi:10.1158/1078-0432.CCR-14-2650. ISSN 1557-3265. PMC 4537825. PMID 25957288.
- ↑ 59.0 59.1 Parker, Matthew; et al. (2014-02-27). "C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma". Nature. 506 (7489): 451–455. doi:10.1038/nature13109. ISSN 1476-4687. PMC 4050669. PMID 24553141.
- ↑ 60.0 60.1 60.2 60.3 Northcott, Paul A.; et al. (2012-08-02). "Subgroup-specific structural variation across 1,000 medulloblastoma genomes". Nature. 488 (7409): 49–56. doi:10.1038/nature11327. ISSN 1476-4687. PMC 3683624. PMID 22832581.
- ↑ 61.0 61.1 61.2 61.3 Shih, David J. H.; et al. (2014-03-20). "Cytogenetic prognostication within medulloblastoma subgroups". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 32 (9): 886–896. doi:10.1200/JCO.2013.50.9539. ISSN 1527-7755. PMC 3948094. PMID 24493713.
- ↑ 62.0 62.1 62.2 62.3 Taylor, Michael D.; et al. (2012-04). "Molecular subgroups of medulloblastoma: the current consensus". Acta Neuropathologica. 123 (4): 465–472. doi:10.1007/s00401-011-0922-z. ISSN 1432-0533. PMC 3306779. PMID 22134537. Check date values in:
|date=(help) - ↑ Goschzik, Tobias; et al. (2015-02). "Molecular stratification of medulloblastoma: comparison of histological and genetic methods to detect Wnt activated tumours". Neuropathology and Applied Neurobiology. 41 (2): 135–144. doi:10.1111/nan.12161. ISSN 1365-2990. PMID 24894640. Check date values in:
|date=(help) - ↑ Ellison, David W.; et al. (2005-11-01). "beta-Catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children's Cancer Study Group Brain Tumour Committee". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 23 (31): 7951–7957. doi:10.1200/JCO.2005.01.5479. ISSN 0732-183X. PMID 16258095.
- ↑ 65.0 65.1 65.2 65.3 Kool, Marcel; et al. (2012-04). "Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas". Acta Neuropathologica. 123 (4): 473–484. doi:10.1007/s00401-012-0958-8. ISSN 1432-0533. PMC 3306778. PMID 22358457. Check date values in:
|date=(help) - ↑ 66.0 66.1 66.2 66.3 Northcott, Paul A.; et al. (2014-07-24). "Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma". Nature. 511 (7510): 428–434. doi:10.1038/nature13379. ISSN 1476-4687. PMC 4201514. PMID 25043047.
- ↑ 67.0 67.1 67.2 67.3 Pugh, Trevor J.; et al. (2012-08-02). "Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations". Nature. 488 (7409): 106–110. doi:10.1038/nature11329. ISSN 1476-4687. PMC 3413789. PMID 22820256.
- ↑ 68.0 68.1 68.2 68.3 68.4 68.5 68.6 Thompson, Eric M.; et al. (2016-04). "Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis". The Lancet. Oncology. 17 (4): 484–495. doi:10.1016/S1470-2045(15)00581-1. ISSN 1474-5488. PMC 4907853. PMID 26976201. Check date values in:
|date=(help) - ↑ Northcott, Paul A.; et al. (2011-04-10). "Medulloblastoma comprises four distinct molecular variants". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 29 (11): 1408–1414. doi:10.1200/JCO.2009.27.4324. ISSN 1527-7755. PMC 4874239. PMID 20823417.
- ↑ 70.0 70.1 70.2 70.3 Rausch, Tobias; et al. (2012-01-20). "Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations". Cell. 148 (1–2): 59–71. doi:10.1016/j.cell.2011.12.013. ISSN 1097-4172. PMC 3332216. PMID 22265402.
- ↑ 71.0 71.1 71.2 71.3 Northcott, Paul A; et al. (2012-12). "Medulloblastomics: The End of the Beginning". Nature reviews. Cancer. 12 (12): 818–834. doi:10.1038/nrc3410. ISSN 1474-175X. PMC 3889646. PMID 23175120. Check date values in:
|date=(help) - ↑ 72.0 72.1 72.2 72.3 Thompson, Margaret C.; et al. (2006-04-20). "Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 24 (12): 1924–1931. doi:10.1200/JCO.2005.04.4974. ISSN 1527-7755. PMID 16567768.
- ↑ 73.0 73.1 73.2 73.3 Rutkowski, Stefan; et al. (2010-11-20). "Survival and prognostic factors of early childhood medulloblastoma: an international meta-analysis". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 28 (33): 4961–4968. doi:10.1200/JCO.2010.30.2299. ISSN 1527-7755. PMID 20940197.
- ↑ Kool, Marcel; et al. (2014-03-17). "Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition". Cancer Cell. 25 (3): 393–405. doi:10.1016/j.ccr.2014.02.004. ISSN 1878-3686. PMC 4493053. PMID 24651015.
- ↑ Northcott, Paul A.; et al. (2011-08). "Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct". Acta Neuropathologica. 122 (2): 231–240. doi:10.1007/s00401-011-0846-7. ISSN 1432-0533. PMC 4538327. PMID 21681522. Check date values in:
|date=(help) - ↑ Gajjar, Amar; et al. (2013-11-15). "Phase I study of vismodegib in children with recurrent or refractory medulloblastoma: a pediatric brain tumor consortium study". Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 19 (22): 6305–6312. doi:10.1158/1078-0432.CCR-13-1425. ISSN 1557-3265. PMC 3856244. PMID 24077351.
- ↑ Spence, Tara; et al. (2014-08). "CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity". Acta Neuropathologica. 128 (2): 291–303. doi:10.1007/s00401-014-1291-1. ISSN 1432-0533. PMC 4159569. PMID 24839957. Check date values in:
|date=(help) - ↑ Gessi, Marco; et al. (2014-07). "MYCN amplification predicts poor outcome for patients with supratentorial primitive neuroectodermal tumors of the central nervous system". Neuro-Oncology. 16 (7): 924–932. doi:10.1093/neuonc/not302. ISSN 1523-5866. PMC 4057132. PMID 24470553. Check date values in:
|date=(help) - ↑ Korshunov, Andrey; et al. (2014-08). "Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity". Acta Neuropathologica. 128 (2): 279–289. doi:10.1007/s00401-013-1228-0. ISSN 1432-0533. PMC 4102829. PMID 24337497. Check date values in:
|date=(help) - ↑ Nobusawa, Sumihito; et al. (2012-09). "Analysis of chromosome 19q13.42 amplification in embryonal brain tumors with ependymoblastic multilayered rosettes". Brain Pathology (Zurich, Switzerland). 22 (5): 689–697. doi:10.1111/j.1750-3639.2012.00574.x. ISSN 1750-3639. PMID 22324795. Check date values in:
|date=(help) - ↑ Korshunov, Andrey; et al. (2010-08). "Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes". Acta Neuropathologica. 120 (2): 253–260. doi:10.1007/s00401-010-0688-8. ISSN 1432-0533. PMID 20407781. Check date values in:
|date=(help) - ↑ Pfister, Stefan; et al. (2009-04). "Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes". Acta Neuropathologica. 117 (4): 457–464. doi:10.1007/s00401-008-0467-y. ISSN 1432-0533. PMID 19057917. Check date values in:
|date=(help) - ↑ Sturm, Dominik; et al. (2016-02-25). "New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs". Cell. 164 (5): 1060–1072. doi:10.1016/j.cell.2016.01.015. ISSN 1097-4172. PMC 5139621. PMID 26919435.
- ↑ Picard, Daniel; et al. (2012-08). "Markers of survival and metastatic potential in childhood CNS primitive neuro-ectodermal brain tumours: an integrative genomic analysis". The Lancet. Oncology. 13 (8): 838–848. doi:10.1016/S1470-2045(12)70257-7. ISSN 1474-5488. PMC 3615440. PMID 22691720. Check date values in:
|date=(help) - ↑ von Bueren, André O.; et al. (2012-09). "DNA copy number alterations in central primitive neuroectodermal tumors and tumors of the pineal region: an international individual patient data meta-analysis". Journal of Neuro-Oncology. 109 (2): 415–423. doi:10.1007/s11060-012-0911-7. ISSN 1573-7373. PMID 22772606. Check date values in:
|date=(help) - ↑ Safaee, Michael; et al. (2013-03). "Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis". Neuro-Oncology. 15 (3): 255–267. doi:10.1093/neuonc/nos289. ISSN 1523-5866. PMC 3578480. PMID 23172371. Check date values in:
|date=(help) - ↑ 87.0 87.1 Japp, Anna Sophia; et al. (2015-02). "High-resolution genomic analysis does not qualify atypical plexus papilloma as a separate entity among choroid plexus tumors". Journal of Neuropathology and Experimental Neurology. 74 (2): 110–120. doi:10.1097/NEN.0000000000000154. ISSN 1554-6578. PMID 25575132. Check date values in:
|date=(help) - ↑ 88.0 88.1 Merino, Diana M.; et al. (2015-01-01). "Molecular characterization of choroid plexus tumors reveals novel clinically relevant subgroups". Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 21 (1): 184–192. doi:10.1158/1078-0432.CCR-14-1324. ISSN 1557-3265. PMID 25336695.
- ↑ Rickert, Christian H.; et al. (2002-03). "Chromosomal imbalances in choroid plexus tumors". The American Journal of Pathology. 160 (3): 1105–1113. doi:10.1016/S0002-9440(10)64931-0. ISSN 0002-9440. PMC 1867193. PMID 11891207. Check date values in:
|date=(help) - ↑ Ruland, Vincent; et al. (2014-05). "Choroid plexus carcinomas are characterized by complex chromosomal alterations related to patient age and prognosis". Genes, Chromosomes & Cancer. 53 (5): 373–380. doi:10.1002/gcc.22148. ISSN 1098-2264. PMID 24478045. Check date values in:
|date=(help) - ↑ Gozali, Alexa E.; et al. (2012-06). "Choroid plexus tumors; management, outcome, and association with the Li-Fraumeni syndrome: the Children's Hospital Los Angeles (CHLA) experience, 1991-2010". Pediatric Blood & Cancer. 58 (6): 905–909. doi:10.1002/pbc.23349. ISSN 1545-5017. PMID 21990040. Check date values in:
|date=(help) - ↑ Nupponen, Nina N.; et al. (2008-03). "Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 21 (3): 265–270. doi:10.1038/modpathol.3800989. ISSN 0893-3952. PMID 18157090. Check date values in:
|date=(help) - ↑ Theeler, Brett J.; et al. (2014-06). "Adult pilocytic astrocytomas: clinical features and molecular analysis". Neuro-Oncology. 16 (6): 841–847. doi:10.1093/neuonc/not246. ISSN 1523-5866. PMC 4022218. PMID 24470550. Check date values in:
|date=(help) - ↑ Strowd, Roy E.; et al. (2016-06). "Histologically benign, clinically aggressive: Progressive non-optic pathway pilocytic astrocytomas in adults with NF1". American Journal of Medical Genetics. Part A. 170 (6): 1455–1461. doi:10.1002/ajmg.a.37622. ISSN 1552-4833. PMC 4938896. PMID 26992069. Check date values in:
|date=(help) - ↑ 95.0 95.1 95.2 Chappé, Céline; et al. (2013-09). "Dysembryoplastic neuroepithelial tumors share with pleomorphic xanthoastrocytomas and gangliogliomas BRAF(V600E) mutation and expression". Brain Pathology (Zurich, Switzerland). 23 (5): 574–583. doi:10.1111/bpa.12048. ISSN 1750-3639. PMID 23442159. Check date values in:
|date=(help) - ↑ Vaubel, Rachael A.; et al. (2018-03). "Recurrent copy number alterations in low-grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation". Brain Pathology (Zurich, Switzerland). 28 (2): 172–182. doi:10.1111/bpa.12495. ISSN 1750-3639. PMC 5807227. PMID 28181325. Check date values in:
|date=(help) - ↑ Prabowo, Avanita S.; et al. (2015-10). "Landscape of chromosomal copy number aberrations in gangliogliomas and dysembryoplastic neuroepithelial tumours". Neuropathology and Applied Neurobiology. 41 (6): 743–755. doi:10.1111/nan.12235. ISSN 1365-2990. PMID 25764012. Check date values in:
|date=(help) - ↑ Rivera, Barbara; et al. (2016-06). "Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors". Acta Neuropathologica. 131 (6): 847–863. doi:10.1007/s00401-016-1549-x. ISSN 1432-0533. PMC 5039033. PMID 26920151. Check date values in:
|date=(help) - ↑ Thom, Maria; et al. (2011-10). "One hundred and one dysembryoplastic neuroepithelial tumors: an adult epilepsy series with immunohistochemical, molecular genetic, and clinical correlations and a review of the literature". Journal of Neuropathology and Experimental Neurology. 70 (10): 859–878. doi:10.1097/NEN.0b013e3182302475. ISSN 1554-6578. PMID 21937911. Check date values in:
|date=(help) - ↑ Kitamura, Yohei; et al. (2018-01). "Comprehensive genetic characterization of rosette-forming glioneuronal tumors: independent component analysis by tissue microdissection". Brain Pathology (Zurich, Switzerland). 28 (1): 87–93. doi:10.1111/bpa.12468. ISSN 1750-3639. PMID 27893178. Check date values in:
|date=(help) - ↑ Bidinotto, Lucas Tadeu; et al. (2015). "Molecular Profiling of a Rare Rosette-Forming Glioneuronal Tumor Arising in the Spinal Cord". PloS One. 10 (9): e0137690. doi:10.1371/journal.pone.0137690. ISSN 1932-6203. PMC 4570813. PMID 26371886.
- ↑ 102.0 102.1 Eckel-Passow, Jeanette E.; et al. (2015-06-25). "Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors". The New England Journal of Medicine. 372 (26): 2499–2508. doi:10.1056/NEJMoa1407279. ISSN 1533-4406. PMC 4489704. PMID 26061753.
- ↑ 103.0 103.1 Neill, Stewart G.; et al. (2014-09-XX). "Section III: molecular diagnostics in neuro-oncology". Current Problems in Cancer. 38 (5): 175–179. doi:10.1016/j.currproblcancer.2014.08.006. ISSN 1535-6345. PMID 25263767. Check date values in:
|date=(help) - ↑ 104.0 104.1 104.2 104.3 104.4 Ellison, David W. (2015-06-25). "Multiple Molecular Data Sets and the Classification of Adult Diffuse Gliomas". The New England Journal of Medicine. 372 (26): 2555–2557. doi:10.1056/NEJMe1506813. ISSN 1533-4406. PMID 26061754.
- ↑ 105.0 105.1 105.2 105.3 Park, Sung-Hye; et al. (2017-05). "Molecular Testing of Brain Tumor". Journal of Pathology and Translational Medicine. 51 (3): 205–223. doi:10.4132/jptm.2017.03.08. ISSN 2383-7837. PMC 5445205. PMID 28535583. Check date values in:
|date=(help) - ↑ 106.0 106.1 106.2 106.3 Cohen, Adam; et al. (2015-06-20). "DNA copy number analysis of Grade II-III and Grade IV gliomas reveals differences in molecular ontogeny including chromothripsis associated with IDH mutation status". Acta Neuropathologica Communications. 3: 34. doi:10.1186/s40478-015-0213-3. ISSN 2051-5960. PMC 4474351. PMID 26091668.
- ↑ Olar, Adriana; et al. (2015-04). "IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas". Acta Neuropathologica. 129 (4): 585–596. doi:10.1007/s00401-015-1398-z. ISSN 1432-0533. PMC 4369189. PMID 25701198. Check date values in:
|date=(help) - ↑ Lhotska, Halka; et al. (2016). "Primary and recurrent diffuse astrocytomas: genomic profile comparison reveals acquisition of biologically relevant aberrations". Molecular Cytogenetics. 9: 13. doi:10.1186/s13039-016-0222-3. ISSN 1755-8166. PMC 4748601. PMID 26865861.
- ↑ Qaddoumi, Ibrahim; et al. (2016-06). "Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology". Acta Neuropathologica. 131 (6): 833–845. doi:10.1007/s00401-016-1539-z. ISSN 1432-0533. PMC 4866893. PMID 26810070. Check date values in:
|date=(help) - ↑ Kamoun, Aurélie; et al. (2016-04-19). "Integrated multi-omics analysis of oligodendroglial tumours identifies three subgroups of 1p/19q co-deleted gliomas". Nature Communications. 7: 11263. doi:10.1038/ncomms11263. ISSN 2041-1723. PMC 4838899. PMID 27090007.
- ↑ Alentorn, Agustí; et al. (2014-03). "Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas". Neuro-Oncology. 16 (3): 400–408. doi:10.1093/neuonc/not227. ISSN 1523-5866. PMC 3922518. PMID 24335697. Check date values in:
|date=(help) - ↑ Rice, Terri; et al. (2016-03). "Understanding inherited genetic risk of adult glioma - a review". Neuro-Oncology Practice. 3 (1): 10–16. doi:10.1093/nop/npv026. ISSN 2054-2577. PMC 4774334. PMID 26941959. Check date values in:
|date=(help) - ↑ 113.0 113.1 Geisenberger, Christoph; et al. (2015-09). "Molecular profiling of long-term survivors identifies a subgroup of glioblastoma characterized by chromosome 19/20 co-gain". Acta Neuropathologica. 130 (3): 419–434. doi:10.1007/s00401-015-1427-y. ISSN 1432-0533. PMID 25931051. Check date values in:
|date=(help) - ↑ 114.0 114.1 Louis, David N.; et al. (2016-06). "The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary". Acta Neuropathologica. 131 (6): 803–820. doi:10.1007/s00401-016-1545-1. ISSN 1432-0533. PMID 27157931. Check date values in:
|date=(help) - ↑ Liu, Qun; et al. (2015-10). "Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma". Acta Neuropathologica. 130 (4): 587–597. doi:10.1007/s00401-015-1470-8. ISSN 1432-0533. PMC 4776337. PMID 26323991. Check date values in:
|date=(help) - ↑ 116.0 116.1 116.2 Och, Waldemar; et al. (2016-11-XX). "Recurrence-associated chromosomal anomalies in meningiomas: Single-institution study and a systematic review with meta-analysis". Neurologia I Neurochirurgia Polska. 50 (6): 439–448. doi:10.1016/j.pjnns.2016.08.003. ISSN 0028-3843. PMID 27575681. Check date values in:
|date=(help) - ↑ 117.0 117.1 117.2 117.3 117.4 Lee, Yohan; et al. (2010-07). "Genomic landscape of meningiomas". Brain Pathology (Zurich, Switzerland). 20 (4): 751–762. doi:10.1111/j.1750-3639.2009.00356.x. ISSN 1750-3639. PMC 3167483. PMID 20015288. Check date values in:
|date=(help) - ↑ Jansen, M.; et al. (2012-04). "Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival". Neuropathology and Applied Neurobiology. 38 (2): 213–219. doi:10.1111/j.1365-2990.2011.01222.x. ISSN 1365-2990. PMC 3563294. PMID 21988727. Check date values in:
|date=(help) - ↑ 119.0 119.1 119.2 Gabeau-Lacet, Darlene; et al. (2009-10). "Genomic profiling of atypical meningiomas associates gain of 1q with poor clinical outcome". Journal of Neuropathology and Experimental Neurology. 68 (10): 1155–1165. doi:10.1097/NEN.0b013e3181ba3952. ISSN 1554-6578. PMC 2847373. PMID 19918127. Check date values in:
|date=(help) - ↑ 120.0 120.1 120.2 Abedalthagafi, Malak S.; et al. (2014-11-15). "Angiomatous meningiomas have a distinct genetic profile with multiple chromosomal polysomies including polysomy of chromosome 5". Oncotarget. 5 (21): 10596–10606. doi:10.18632/oncotarget.2517. ISSN 1949-2553. PMC 4279396. PMID 25347344.
- ↑ 121.0 121.1 121.2 Brastianos, Priscilla K.; et al. (2013-03). "Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations". Nature Genetics. 45 (3): 285–289. doi:10.1038/ng.2526. ISSN 1546-1718. PMC 3739288. PMID 23334667. Check date values in:
|date=(help) - ↑ 122.0 122.1 122.2 Abedalthagafi, Malak S.; et al. (2015-06). "ARID1A and TERT promoter mutations in dedifferentiated meningioma". Cancer Genetics. 208 (6): 345–350. doi:10.1016/j.cancergen.2015.03.005. ISSN 2210-7762. PMC 4882906. PMID 25963524. Check date values in:
|date=(help) - ↑ 123.0 123.1 123.2 Abedalthagafi, Malak; et al. (2016-05). "Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma". Neuro-Oncology. 18 (5): 649–655. doi:10.1093/neuonc/nov316. ISSN 1523-5866. PMC 4827048. PMID 26826201. Check date values in:
|date=(help) - ↑ 124.0 124.1 124.2 Harmancı, Akdes Serin; et al. (2017-02-14). "Integrated genomic analyses of de novo pathways underlying atypical meningiomas". Nature Communications. 8: 14433. doi:10.1038/ncomms14433. ISSN 2041-1723. PMC 5316884. PMID 28195122.
- ↑ 125.0 125.1 125.2 Aizer, Ayal A.; et al. (2016-02). "A prognostic cytogenetic scoring system to guide the adjuvant management of patients with atypical meningioma". Neuro-Oncology. 18 (2): 269–274. doi:10.1093/neuonc/nov177. ISSN 1523-5866. PMC 4724184. PMID 26323607. Check date values in:
|date=(help) - ↑ 126.0 126.1 126.2 Büschges, Rainer; et al. (2002-04). "Allelic gain and amplification on the long arm of chromosome 17 in anaplastic meningiomas". Brain Pathology (Zurich, Switzerland). 12 (2): 145–153. doi:10.1111/j.1750-3639.2002.tb00429.x. ISSN 1015-6305. PMID 11958368. Check date values in:
|date=(help) - ↑ 127.0 127.1 127.2 Domingues, Patrícia; et al. (2015-05-10). "Genetic/molecular alterations of meningiomas and the signaling pathways targeted". Oncotarget. 6 (13): 10671–10688. doi:10.18632/oncotarget.3870. ISSN 1949-2553. PMC 4484411. PMID 25965831.
- ↑ 128.0 128.1 128.2 Domingues, Patrícia Henriques; et al. (2014-05). "Proposal for a new risk stratification classification for meningioma based on patient age, WHO tumor grade, size, localization, and karyotype". Neuro-Oncology. 16 (5): 735–747. doi:10.1093/neuonc/not325. ISSN 1523-5866. PMC 3984558. PMID 24536048. Check date values in:
|date=(help) - ↑ 129.0 129.1 129.2 Linsler, Stefan; et al. (2014). "Molecular biological determinations of meningioma progression and recurrence". PloS One. 9 (4): e94987. doi:10.1371/journal.pone.0094987. ISSN 1932-6203. PMC 3983248. PMID 24722350.
- ↑ 130.0 130.1 130.2 Arslantas, Ali; et al. (2003-01). "Detection of chromosomal imbalances in spinal meningiomas by comparative genomic hybridization". Neurologia Medico-Chirurgica. 43 (1): 12–18, discussion 19. doi:10.2176/nmc.43.12. ISSN 0470-8105. PMID 12568317. Check date values in:
|date=(help) - ↑ 131.0 131.1 131.2 Bi, Wenya Linda; et al. (2016-09). "Genomic landscape of intracranial meningiomas". Journal of Neurosurgery. 125 (3): 525–535. doi:10.3171/2015.6.JNS15591. ISSN 1933-0693. PMID 26771848. Check date values in:
|date=(help) - ↑ 132.0 132.1 132.2 Bi, Wenya Linda; et al. (2016-04). "Genomic and Epigenomic Landscape in Meningioma". Neurosurgery Clinics of North America. 27 (2): 167–179. doi:10.1016/j.nec.2015.11.009. ISSN 1558-1349. PMID 27012381. Check date values in:
|date=(help) - ↑ 133.0 133.1 133.2 Och, Waldemar; et al. (2016-11-XX). "The correlation of clinical and chromosomal alterations of benign meningiomas and their recurrences". Neurologia I Neurochirurgia Polska. 50 (6): 395–402. doi:10.1016/j.pjnns.2016.07.001. ISSN 0028-3843. PMID 27480481. Check date values in:
|date=(help) - ↑ 134.0 134.1 134.2 Yuzawa, Sayaka; et al. (2016-10). "Genetic landscape of meningioma". Brain Tumor Pathology. 33 (4): 237–247. doi:10.1007/s10014-016-0271-7. ISSN 1861-387X. PMID 27624470. Check date values in:
|date=(help) - ↑ 135.0 135.1 135.2 Bi, Wenya Linda; et al. (2016). "Meningioma Genomics: Diagnostic, Prognostic, and Therapeutic Applications". Frontiers in Surgery. 3: 40. doi:10.3389/fsurg.2016.00040. ISSN 2296-875X. PMC 4933705. PMID 27458586.
- ↑ 136.0 136.1 136.2 Ketter, Ralf; et al. (2007-06). "Hyperdiploidy defines a distinct cytogenetic entity of meningiomas". Journal of Neuro-Oncology. 83 (2): 213–221. doi:10.1007/s11060-006-9318-7. ISSN 0167-594X. PMID 17225936. Check date values in:
|date=(help) - ↑ Wu, Jing; et al. (2016-07). "Biology and management of ependymomas". Neuro-Oncology. 18 (7): 902–913. doi:10.1093/neuonc/now016. ISSN 1523-5866. PMC 4896548. PMID 27022130. Check date values in:
|date=(help)