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Recurrent Genomic Alterations in Pediatric and Adult Central Nervous System Tumors Detected by Chromosomal Microarray (view source)
Revision as of 12:44, 15 April 2021
, 12:44, 15 April 2021adding citations
{| 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'''
|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 PMID:25664944; PMID:26378811 PMCID:3429698; PMID:23817572; PMID:23583981 PMID:18974108; PMID:23278243; 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
|PMID:26829751; PMID:23633565; PMID:26778052 PMID:23583981
|-
|-
|
|
| Ganglioglioma
|Ganglioglioma
| Only 30% are abnormal by karyotype <br>
|Only 30% are abnormal by karyotype <br>
'''Gain:''' polysomy 7
'''Gain:''' polysomy 7
| '''Mutations:''' BRAF V600E in 20-60% of cases (can be concurrent with CDKN2A homozygous deletion)<br>
|'''Mutations:''' BRAF V600E in 20-60% of cases (can be concurrent with CDKN2A homozygous deletion)<br>
'''Fusions:''' KIAA1549-BRAF
'''Fusions:''' KIAA1549-BRAF
| Generally indolent tumors for which surgical resection can be curative
|Generally indolent tumors for which surgical resection can be curative
| PMID:25461780; PMID:23583981; PMID:11996800 PMID:23609006; PMID:29880043
|<ref name=":0" />PMID:25461780; PMID:23583981; PMID:11996800 PMID:23609006; 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
|PMID:25664944; PMID:23633565; PMID:26061751 PMID:26824661; PMID:26004297; <ref name=":0" />PMID:25461780 PMID:23583981
|-
|-
|
|
| Pleomorphic xanthoastrocytoma (PXA)
|Pleomorphic xanthoastrocytoma (PXA)
| Polysomy 3, polysomy 7 observed<br>
|Polysomy 3, polysomy 7 observed<br>
'''Loss:''' monosomy 9 / 9p deletion
'''Loss:''' monosomy 9 / 9p deletion
| '''Mutations:''' BRAF V600E in ~60%; TP53 (5%)<br>
|'''Mutations:''' BRAF V600E in ~60%; TP53 (5%)<br>
'''Loss:''' CDKN2A/CDKN2B
'''Loss:''' CDKN2A/CDKN2B
|
|
| PMID:25461780; PMID:23583981; PMID:16909113; PMID:12484572
|<ref name=":0" />PMID:25461780; PMID:23583981; PMID:16909113; 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
|PMCID:1891902; PMID:26004297; <ref name=":0" />PMID:25461780; PMID:24140581; PMCID:5323185; PMID:27230974 PMID:27196377; PMID:26061751; PMID:25962792; 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<br>
|'''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
PMID:25318587; PMID:23096133; PMID:21274720
|-
|-
|Glioblastoma, WHO grade IV
|Glioblastoma, WHO grade IV
|IDH-mutant
|IDH-mutant
|'''Gain:''' 1q, 2q, 3q, 7, 16p, 17q, 21q<br>
|'''Gain:''' 1q, 2q, 3q, 7, 16p, 17q, 21q<br>
'''Loss:''' 6q, 8q, 9p, 9q, 10q, 13q, 17p, 22q<br>
'''Loss:''' 6q, 8q, 9p, 9q, 10q, 13q, 17p, 22q<br>
'''Amplification:''' PDGFRA, MYCN, MET, CDK4, CDK6 (EGFR, MDM2 amp rare)<br>
'''Amplification:''' PDGFRA, MYCN, MET, CDK4, CDK6 (EGFR, MDM2 amp rare)<br>
'''Mutations:''' IDH1/2 (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
'''Mutations:''' IDH1/2 (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; PMID:29687258; PMID:20479398; PMID:24959384
|PMID:25752754; PMID:25727226; PMID:26328271; PMID:22837387; PMID:25754088; <ref name=":0" />PMID:25461780; PMCID:1891902; PMID:23417712; PMCID:5323185; PMID:29687258; PMID:20479398; PMID:24959384
|-
|-
|Diffuse midline glioma, H3 K27M mutant
|Diffuse midline glioma, H3 K27M mutant
|-
|-
|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
|-
|-
|
|
|SHH-activated
|SHH-activated
|'''Gain:''' 3q<br>
|'''Gain:''' 3q<br>
'''Loss:''' 9q, 10q, 17p<br>
'''Loss:''' 9q, 10q, 17p<br>
|'''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 PMID:23175120; PMID:22134537; PMID:22832581; PMID:24493713; PMID:22358457; PMID:25043047 PMID:22820256; PMID:26976201; PMID:20823417 PMID:22265402; PMCID:3889646; PMID:16567768 PMID:20940197; PMID:23175120
|PMID:22832581, PMID:25043047; PMID:24493713 PMID:23175120; PMID:22134537; PMID:22832581; PMID:24493713; PMID:22358457; PMID:25043047 PMID:22820256; PMID:26976201; PMID:20823417 PMID:22265402; PMCID:3889646; PMID:16567768 PMID:20940197; PMID:23175120
|-
|-
|
|
'''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 PMID:23175120; PMID:22134537; PMID:22832581; PMID:24493713; PMID:22358457; PMID:25043047 PMID:22820256; PMID:26976201; PMID:20823417 PMID:22265402; PMCID:3889646; PMID:16567768 PMID:20940197 PMID:23175120
|PMID:22832581; PMID:25043047; PMID:24493713 PMID:23175120; PMID:22134537; PMID:22832581; PMID:24493713; PMID:22358457; PMID:25043047 PMID:22820256; PMID:26976201; PMID:20823417 PMID:22265402; PMCID:3889646; PMID:16567768 PMID:20940197 PMID:23175120
|-
|-
|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
PMID:24839957; PMID:24470553 PMID:24337497; PMID:22324795 PMID:20407781, PMID:19057917
|-
|-
'''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
PMID:23172371; PMID:25575132; PMID:25336695 PMID:11891207
|'''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
|PMID:24478045; PMID:21990040; PMID:25575132; PMID:18157090; PMID:25336695
|}
|}
{| 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'''
|
|
|-
|-
|Low grade gliomas, WHO grade I-II
|Low grade gliomas, WHO grade I-II
|Pilocytic astrocytoma
|Pilocytic astrocytoma
|'''Gain:''' 5, 7, 6, 11<br>
|'''Gain:''' 5, 7, 6, 11<br>
|'''Loss:''' homozygous loss CDKN2A/B<br>
|'''Loss:''' homozygous loss CDKN2A/B<br>
Mutation: BRAF V600E
Mutation: BRAF V600E
|Adults and pediatric tumors show similar CNVs; CDKN2A/CDKN2B loss may correlate with anaplastic histology
|Adults and pediatric tumors show similar CNVs; CDKN2A/CDKN2B loss may correlate with anaplastic histology
|PMID:23442159; PMID:28181325
|PMID:23442159; PMID:28181325
|-
|-
'''Loss:''' PTEN
'''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.
|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.
|PMID:26061754; PMID:25754088; PMID:28535583 PMID:25931051; PMID:26091668; PMID:25461780; PMID:27157931; PMID:25727226; PMID:26323991 PMID:26061751; PMID:29687258
|PMID:26061754; PMID:25754088; PMID:28535583 PMID:25931051; PMID:26091668; <ref name=":0" />PMID:25461780; PMID:27157931; PMID:25727226; PMID:26323991 PMID:26061751; PMID:29687258
|-
|-
|
|
'''Amplification:''' EGFR, MDM4, MDM2, CDK4, PDGFRA, MET
'''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.
|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.
|PMID:26061754; PMID:25754088; PMID:28535583 PMID:25931051; PMID:26091668; PMID:25461780; PMID:27157931; PMID:25727226; PMID:26061751
|PMID:26061754; PMID:25754088; PMID:28535583 PMID:25931051; PMID:26091668; <ref name=":0" />PMID:25461780; PMID:27157931; PMID:25727226; PMID:26061751
|-
|-
|'''MENINGIOMA'''
|'''MENINGIOMA'''
|-
|-
|
|
|Grade 1
|Grade 1
|No copy number changes in 44%<br>
|No copy number changes in 44%<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 not reliable; 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 not reliable; 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
PMID:25965575; PMID:21627842; PMID:24939246; PMID:22516549
|Myxopapillary ependymoma, WHO grade I (spinal)
|Myxopapillary ependymoma, WHO grade I (spinal)
|'''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
|More common in adults
|More common in adults
|PMID:25965575; PMCID:3991130; PMID:20425037 PMID:25957288; PMID:25965575; PMID:22516549
|PMID:25965575; PMCID:3991130; PMID:20425037 PMID:25957288; PMID:25965575; PMID:22516549
|Mostly intracranial tumors, rarely in spinal cord
|Mostly intracranial tumors, rarely in spinal cord
|PMID: 25965575; PMID:27022130
|PMID: 25965575; PMID:27022130
|}