Line 100: |
Line 100: |
| | - also seen in PLNTY, ganglioglioma, and pilocytic astrocytoma; can distinguish by methylation signature<ref name=":0" /> | | | - also seen in PLNTY, ganglioglioma, and pilocytic astrocytoma; can distinguish by methylation signature<ref name=":0" /> |
| | | |
− | - in-frame fusion<ref name=":6" /> | + | - in-frame fusion<ref name=":6" /> |
| |- | | |- |
| |t(8;8)(p11.23;p11.22)<ref name=":6" /><ref name=":7" /> | | |t(8;8)(p11.23;p11.22)<ref name=":6" /><ref name=":7" /> |
Line 183: |
Line 183: |
| {| class="wikitable" | | {| class="wikitable" |
| |'''Chr # ''' | | |'''Chr # ''' |
− | |'''Gain/Loss/Amp/LOH''' | + | |'''Gain/Loss/Amp/LOH''' |
− | |'''Minimal Region Genomic Coordinates [Genome Build]''' | + | |'''Minimal Region Genomic Coordinates [Genome Build]''' |
− | |'''Minimal Region Cytoband''' | + | |'''Minimal Region Cytoband''' |
− | |'''Diagnostic Significance (Yes, No or Unknown)''' | + | |'''Diagnostic Significance (Yes, No or Unknown)''' |
| |'''Prognostic Significance''' | | |'''Prognostic Significance''' |
| | | |
Line 192: |
Line 192: |
| |'''Therapeutic Significance''' | | |'''Therapeutic Significance''' |
| | | |
− | '''(Yes, No or Unknown)''' | + | '''(Yes, No or Unknown)''' |
− | |'''Notes''' | + | |'''Notes''' |
| |- | | |- |
− | |1 | + | |1 |
− | |loss | + | |loss |
| |Chr1:1- 248956422 | | |Chr1:1- 248956422 |
| <br /> | | <br /> |
− | |Chr1 | + | |Chr1 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| | colspan="1" rowspan="20" |This constellation of chromosomal abnormalities was found in a case series of 40 gangliogliomas[8]. | | | colspan="1" rowspan="20" |This constellation of chromosomal abnormalities was found in a case series of 40 gangliogliomas[8]. |
| | | |
| It is unknown if the abnormalities are either diagnostic, prognostic or therapeutic. | | It is unknown if the abnormalities are either diagnostic, prognostic or therapeutic. |
| |- | | |- |
− | |3 | + | |3 |
− | |gain | + | |gain |
| |Chr3:1- 198295559 | | |Chr3:1- 198295559 |
| <br /> | | <br /> |
− | |Chr3 | + | |Chr3 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |4 | + | |4 |
− | |gain | + | |gain |
− | |Chr4:1- 190214555 | + | |Chr4:1- 190214555 |
− | |Chr4 | + | |Chr4 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |5 | + | |5 |
− | |gain | + | |gain |
− | |Chr5:1- 181538259 | + | |Chr5:1- 181538259 |
− | |Chr5 | + | |Chr5 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |6 | + | |6 |
− | |gain | + | |gain |
− | |Chr6:1- 170805979 | + | |Chr6:1- 170805979 |
− | |Chr6 | + | |Chr6 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |7 | + | |7 |
− | |gain | + | |gain |
− | |Chr7:1- 159345973 | + | |Chr7:1- 159345973 |
− | |Chr7 | + | |Chr7 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |8 | + | |8 |
− | |gain | + | |gain |
− | |Chr8:1- 145138636 | + | |Chr8:1- 145138636 |
− | |Chr8 | + | |Chr8 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |9 | + | |9 |
− | |gain | + | |gain |
− | |Chr9:1- 138394717 | + | |Chr9:1- 138394717 |
− | |Chr9 | + | |Chr9 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |10 | + | |10 |
− | |loss (segmental) | + | |loss (segmental) |
− | |Chr10:1- 133797422 | + | |Chr10:1- 133797422 |
− | |Chr10 | + | |Chr10 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |11 | + | |11 |
− | |gain | + | |gain |
− | |Chr11:1- 135086622 | + | |Chr11:1- 135086622 |
− | |Chr11 | + | |Chr11 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |12 | + | |12 |
− | |gain | + | |gain |
− | |Chr12:1- 133275309 | + | |Chr12:1- 133275309 |
− | |Chr12 | + | |Chr12 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |15 | + | |15 |
− | |gain | + | |gain |
− | |Chr15: 1- 101991189 | + | |Chr15: 1- 101991189 |
− | |Chr15 | + | |Chr15 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |16 | + | |16 |
| |Gain | | |Gain |
| |Chr16:1-90338345 | | |Chr16:1-90338345 |
| <br /> | | <br /> |
− | |Chr16 | + | |Chr16 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |16 | + | |16 |
− | |loss | + | |loss |
| |Chr16:1-90338345 | | |Chr16:1-90338345 |
| <br /> | | <br /> |
− | |Chr16 | + | |Chr16 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |17 | + | |17 |
− | |loss | + | |loss |
− | |Chr17:1- 83257441 | + | |Chr17:1- 83257441 |
− | |Chr17 | + | |Chr17 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |18 | + | |18 |
− | |gain | + | |gain |
− | |Chr18:1- 80373285 | + | |Chr18:1- 80373285 |
− | |Chr18 | + | |Chr18 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |19 | + | |19 |
− | |gain | + | |gain |
− | |Chr19:1- 58617616 | + | |Chr19:1- 58617616 |
− | |Chr19 | + | |Chr19 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |20 | + | |20 |
− | |gain | + | |gain |
− | |Chr20:1- 64444167 | + | |Chr20:1- 64444167 |
− | |Chr20 | + | |Chr20 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |21 | + | |21 |
− | |gain | + | |gain |
− | |Chr21:1- 46709983 | + | |Chr21:1- 46709983 |
− | |Chr21 | + | |Chr21 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |- | | |- |
− | |22 | + | |22 |
− | |gain | + | |gain |
− | |Chr22:1- 50818468 | + | |Chr22:1- 50818468 |
− | |Chr22 | + | |Chr22 |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
| |} | | |} |
| <br /> | | <br /> |
| ==Gene Mutations (SNV/INDEL)== | | ==Gene Mutations (SNV/INDEL)== |
| {| class="wikitable" | | {| class="wikitable" |
− | |'''Gene; Genetic Alteration''' | + | |'''Gene; Genetic Alteration''' |
− | |'''Presumed Mechanism (Tumor Suppressor Gene (TSG)/Oncogene/Other)''' | + | |'''Presumed Mechanism (Tumor Suppressor Gene (TSG)/Oncogene/Other)''' |
− | |'''Prevalence (COSMIC/ TCGA/Other)''' | + | |'''Prevalence (COSMIC/ TCGA/Other)''' |
− | |'''Concomitant Mutations''' | + | |'''Concomitant Mutations''' |
− | |'''Mutually Exclusive Mutations''' | + | |'''Mutually Exclusive Mutations''' |
− | |'''Diagnostic Significance (Yes, No or Unknown)''' | + | |'''Diagnostic Significance (Yes, No or Unknown)''' |
| |'''Prognostic Significance''' | | |'''Prognostic Significance''' |
| | | |
Line 376: |
Line 376: |
| |'''Therapeutic Significance''' | | |'''Therapeutic Significance''' |
| | | |
− | '''(Yes, No or Unknown)''' | + | '''(Yes, No or Unknown)''' |
− | |'''Notes''' | + | |'''Notes''' |
| |- | | |- |
| |''BRAF'' p.V600E<ref name=":0" /><ref name=":6" /> | | |''BRAF'' p.V600E<ref name=":0" /><ref name=":6" /> |
− | |oncogene | + | |oncogene |
| |10-60%<ref name=":0" /> | | |10-60%<ref name=":0" /> |
| |Homozygous deletion of CDKN2A<ref name=":6" />[8] | | |Homozygous deletion of CDKN2A<ref name=":6" />[8] |
Line 386: |
Line 386: |
| | | |
| H3-3A p.K27M<ref>{{Cite journal|last=Pagès|first=Mélanie|last2=Beccaria|first2=Kevin|last3=Boddaert|first3=Nathalie|last4=Saffroy|first4=Raphaël|last5=Besnard|first5=Aurore|last6=Castel|first6=David|last7=Fina|first7=Frédéric|last8=Barets|first8=Doriane|last9=Barret|first9=Emilie|date=2018-01|title=Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma|url=https://pubmed.ncbi.nlm.nih.gov/27984673|journal=Brain Pathology (Zurich, Switzerland)|volume=28|issue=1|pages=103–111|doi=10.1111/bpa.12473|issn=1750-3639|pmc=8028391|pmid=27984673}}</ref> | | H3-3A p.K27M<ref>{{Cite journal|last=Pagès|first=Mélanie|last2=Beccaria|first2=Kevin|last3=Boddaert|first3=Nathalie|last4=Saffroy|first4=Raphaël|last5=Besnard|first5=Aurore|last6=Castel|first6=David|last7=Fina|first7=Frédéric|last8=Barets|first8=Doriane|last9=Barret|first9=Emilie|date=2018-01|title=Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma|url=https://pubmed.ncbi.nlm.nih.gov/27984673|journal=Brain Pathology (Zurich, Switzerland)|volume=28|issue=1|pages=103–111|doi=10.1111/bpa.12473|issn=1750-3639|pmc=8028391|pmid=27984673}}</ref> |
− | |''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" /> | + | |''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" /> |
− | |Yes<ref name=":0" /><ref name=":6" /> | + | |Yes<ref name=":0" /><ref name=":6" /> |
− | |Yes<ref name=":10">{{Cite journal|last=Ryall|first=Scott|last2=Zapotocky|first2=Michal|last3=Fukuoka|first3=Kohei|last4=Nobre|first4=Liana|last5=Guerreiro Stucklin|first5=Ana|last6=Bennett|first6=Julie|last7=Siddaway|first7=Robert|last8=Li|first8=Christopher|last9=Pajovic|first9=Sanja|date=2020-04-13|title=Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas|url=https://pubmed.ncbi.nlm.nih.gov/32289278|journal=Cancer Cell|volume=37|issue=4|pages=569–583.e5|doi=10.1016/j.ccell.2020.03.011|issn=1878-3686|pmc=7169997|pmid=32289278}}</ref> | + | |Yes<ref name=":10">{{Cite journal|last=Ryall|first=Scott|last2=Zapotocky|first2=Michal|last3=Fukuoka|first3=Kohei|last4=Nobre|first4=Liana|last5=Guerreiro Stucklin|first5=Ana|last6=Bennett|first6=Julie|last7=Siddaway|first7=Robert|last8=Li|first8=Christopher|last9=Pajovic|first9=Sanja|date=2020-04-13|title=Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas|url=https://pubmed.ncbi.nlm.nih.gov/32289278|journal=Cancer Cell|volume=37|issue=4|pages=569–583.e5|doi=10.1016/j.ccell.2020.03.011|issn=1878-3686|pmc=7169997|pmid=32289278}}</ref> |
| |Yes<ref name=":11">{{Cite journal|last=Kowalewski|first=Adam|last2=Durślewicz|first2=Justyna|last3=Zdrenka|first3=Marek|last4=Grzanka|first4=Dariusz|last5=Szylberg|first5=Łukasz|date=2020-08|title=Clinical Relevance of BRAF V600E Mutation Status in Brain Tumors with a Focus on a Novel Management Algorithm|url=https://pubmed.ncbi.nlm.nih.gov/32648041|journal=Targeted Oncology|volume=15|issue=4|pages=531–540|doi=10.1007/s11523-020-00735-9|issn=1776-260X|pmc=7434793|pmid=32648041}}</ref> | | |Yes<ref name=":11">{{Cite journal|last=Kowalewski|first=Adam|last2=Durślewicz|first2=Justyna|last3=Zdrenka|first3=Marek|last4=Grzanka|first4=Dariusz|last5=Szylberg|first5=Łukasz|date=2020-08|title=Clinical Relevance of BRAF V600E Mutation Status in Brain Tumors with a Focus on a Novel Management Algorithm|url=https://pubmed.ncbi.nlm.nih.gov/32648041|journal=Targeted Oncology|volume=15|issue=4|pages=531–540|doi=10.1007/s11523-020-00735-9|issn=1776-260X|pmc=7434793|pmid=32648041}}</ref> |
| |FDA-approved therapy includes dabrafenib-trametinib<ref name=":11" /> | | |FDA-approved therapy includes dabrafenib-trametinib<ref name=":11" /> |
Line 394: |
Line 394: |
| |- | | |- |
| |''BRAF'' indel events: p.L505delinsLEYLS p.R506delinsRVLR p.R506delinsRSTQ p.T599_W604delinsTDG) <ref name=":6" /> | | |''BRAF'' indel events: p.L505delinsLEYLS p.R506delinsRVLR p.R506delinsRSTQ p.T599_W604delinsTDG) <ref name=":6" /> |
− | |oncogene | + | |oncogene |
− | |10%<ref name=":6" /> | + | |10%<ref name=":6" /> |
| | | | | |
− | |''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" /> | + | |''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" /> |
− | |Yes<ref name=":0" /><ref name=":6" /> | + | |Yes<ref name=":0" /><ref name=":6" /> |
− | |Unknown | + | |Unknown |
− | |Unknown | + | |Unknown |
− | | | + | | |
| |- | | |- |
| |''KRAS'' p.Q61K<ref name=":6" /> | | |''KRAS'' p.Q61K<ref name=":6" /> |
− | |oncogene | + | |oncogene |
| |5%<ref name=":6" /> | | |5%<ref name=":6" /> |
| | | | | |
− | |''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" /> | + | |''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" /> |
− | |Yes<ref name=":0" /><ref name=":6" /> | + | |Yes<ref name=":0" /><ref name=":6" /> |
| |No<ref name=":6" /><ref name=":10" /> | | |No<ref name=":6" /><ref name=":10" /> |
− | |No | + | |No |
| | | | | |
| |- | | |- |
| |''FGFR2'' exon 17 splicesite mutation<ref name=":6" /> | | |''FGFR2'' exon 17 splicesite mutation<ref name=":6" /> |
− | |oncogene | + | |oncogene |
| |2.5%<ref name=":6" /> | | |2.5%<ref name=":6" /> |
| <br /> | | <br /> |
| | | | | |
− | |''KRAS, RAF1, NF1, FGFR1, and BRAF''<ref name=":6" /> | + | |''KRAS, RAF1, NF1, FGFR1, and BRAF''<ref name=":6" /> |
− | |Yes<ref name=":0" /><ref name=":6" /> | + | |Yes<ref name=":0" /><ref name=":6" /> |
| |No<ref name=":6" /><ref name=":10" /> | | |No<ref name=":6" /><ref name=":10" /> |
− | |No | + | |No |
| |<nowiki>- no FDA-approved anti-FGFR therapy for ganglioglioma at present </nowiki> | | |<nowiki>- no FDA-approved anti-FGFR therapy for ganglioglioma at present </nowiki> |
| <br /> | | <br /> |
| |- | | |- |
| |''FGFR1'' p.N546K<ref name=":6" /> | | |''FGFR1'' p.N546K<ref name=":6" /> |
− | |oncogene | + | |oncogene |
| |2.5%<ref name=":6" /> | | |2.5%<ref name=":6" /> |
| <br /> | | <br /> |
Line 432: |
Line 432: |
| |''KRAS, RAF1,'' | | |''KRAS, RAF1,'' |
| | | |
− | '' NF1, BRAF, and FGFR2''<ref name=":6" /> | + | '' NF1, BRAF, and FGFR2''<ref name=":6" /> |
− | |Yes<ref name=":0" /><ref name=":6" /> | + | |Yes<ref name=":0" /><ref name=":6" /> |
| |No<ref name=":6" /><ref name=":10" /> | | |No<ref name=":6" /><ref name=":10" /> |
− | |No | + | |No |
| |<nowiki>- no FDA-approved anti-FGFR therapy for ganglioglioma at present </nowiki> | | |<nowiki>- no FDA-approved anti-FGFR therapy for ganglioglioma at present </nowiki> |
| <br /> | | <br /> |
Line 448: |
Line 448: |
| 90% of gangliogliomas harbor genetic alterations activating the MAPK signaling pathway, with non-MAPK signaling seen in 10% of cases (e.g. ''ABL2::GAB2'' gene fusion)<ref name=":6" />. | | 90% of gangliogliomas harbor genetic alterations activating the MAPK signaling pathway, with non-MAPK signaling seen in 10% of cases (e.g. ''ABL2::GAB2'' gene fusion)<ref name=":6" />. |
| {| class="wikitable" | | {| class="wikitable" |
− | |'''Gene; Genetic Alteration''' | + | |'''Gene; Genetic Alteration''' |
− | |'''Pathway''' | + | |'''Pathway''' |
− | |'''Pathophysiologic Outcome''' | + | |'''Pathophysiologic Outcome''' |
| |- | | |- |
− | |BRAF; activating alterations | + | |BRAF; activating alterations |
− | |MAPK signaling | + | |MAPK signaling |
− | |Increased cell growth and proliferation | + | |Increased cell growth and proliferation |
| |- | | |- |
− | |RAF1; activating alterations | + | |RAF1; activating alterations |
− | |MAPK signaling | + | |MAPK signaling |
− | |Increase cell growth and proliferation | + | |Increase cell growth and proliferation |
| |- | | |- |
− | |KRAS; activating mutations | + | |KRAS; activating mutations |
− | |MAPK signaling | + | |MAPK signaling |
− | |Increase cell growth and proliferation | + | |Increase cell growth and proliferation |
| |- | | |- |
− | |NF1; inactivating mutations | + | |NF1; inactivating mutations |
| |MAPK signaling | | |MAPK signaling |
− | |Increase cell growth and proliferation | + | |Increase cell growth and proliferation |
| |- | | |- |
− | |FGFR1/2/3; activating alterations | + | |FGFR1/2/3; activating alterations |
− | |MAPK signaling | + | |MAPK signaling |
− | |Increase cell growth and proliferation | + | |Increase cell growth and proliferation |
| |} | | |} |
| | | |
| ==Diagnostic Testing Methods== | | ==Diagnostic Testing Methods== |
| | | |
− | * Chromosome microarray | + | *Chromosome microarray |
− | * Next generation sequencing | + | *Next generation sequencing |
− | * DNA methylation profiling | + | *DNA methylation profiling |
| | | |
| ==Familial Forms== | | ==Familial Forms== |