Compendium of Cancer Genome Aberrations

CNS5:Astrocytoma, IDH-mutant: Difference between revisions

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{{DISPLAYTITLE:Astrocytoma, IDH-mutant}}


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[[CNS5:Table_of_Contents|Central Nervous System Tumours (WHO Classification, 5th ed.)]]
 
{{Under Construction}}
==Primary Author(s)*==
Meenakshi Mehrotra, PhD, Mount Sinai Health System, New York
==WHO Classification of Disease==
 
{| class="wikitable"
!Structure
!Disease
|-
|Book
|Central Nervous System Tumours (5th ed.)
|-
|Category
|Gliomas, glioneuronal tumours, and neuronal tumours
|-
|Family
|Gliomas, glioneuronal tumours, and neuronal tumours
|-
|Type
|Adult-type diffuse gliomas
|-
|Subtype(s)
|Astrocytoma, IDH-mutant
|}
 
==Related Terminology==
 
{| class="wikitable"
|+
|Acceptable
|N/A
|-
|Not Recommended
|Diffuse astrocytoma, IDH-mutant; anaplastic astrocytoma, IDH-mutant; glioblastoma, IDH-mutant; low-grade astrocytoma; lower-grade astrocytoma; high-grade astrocytoma; infiltrating astrocytoma; diffuse glioma
|}
 
==Gene Rearrangements==
<br />
{| class="wikitable sortable"
|-
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|''MET''
|''PTPRZ1::MET''
|N/A
|N/A
|Rare (~1%)
|P
|No
|MET fusions and splicing variants convergently define a subgroup  of glioma sensitive to MET inhibitors<ref>{{Cite journal|last=Liu|first=Lingyu|last2=Zhang|first2=Ke-Nan|last3=Zhao|first3=Zheng|last4=Li|first4=Guanzhang|last5=Chai|first5=Rui-Chao|last6=Li|first6=Zhuoqun|last7=Liu|first7=Xing|last8=Chen|first8=Jing|last9=Jiang|first9=Tao|date=2024-05|title=MET fusions and splicing variants is a strong adverse prognostic factor in astrocytoma, isocitrate dehydrogenase mutant|url=https://pubmed.ncbi.nlm.nih.gov/37530224|journal=Brain Pathology (Zurich, Switzerland)|volume=34|issue=3|pages=e13198|doi=10.1111/bpa.13198|issn=1750-3639|pmc=11007006|pmid=37530224}}</ref><ref>{{Cite journal|last=Wong|first=Queenie Hoi-Wing|last2=Li|first2=Kay Ka-Wai|last3=Wang|first3=Wei-Wei|last4=Malta|first4=Tathiane M.|last5=Noushmehr|first5=Houtan|last6=Grabovska|first6=Yura|last7=Jones|first7=Chris|last8=Chan|first8=Aden Ka-Yin|last9=Kwan|first9=Johnny Sheung-Him|date=2021-07|title=Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas|url=https://pubmed.ncbi.nlm.nih.gov/33692446|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=34|issue=7|pages=1245–1260|doi=10.1038/s41379-021-00778-x|issn=1530-0285|pmid=33692446}}</ref>
|-
|''NTRK2''
|''GOLGA1::NTRK2''
|N/A
|N/A
|Rare (observed in single case report)
|P, T
|No
|Single case report<ref>{{Cite journal|last=Kirishima|first=Mari|last2=Akahane|first2=Toshiaki|last3=Higa|first3=Nayuta|last4=Suzuki|first4=Shinsuke|last5=Ueno|first5=Shinichi|last6=Yonezawa|first6=Hajime|last7=Uchida|first7=Hiroyuki|last8=Hanaya|first8=Ryosuke|last9=Yoshimoto|first9=Koji|date=2022-11|title=IDH-mutant astrocytoma with an evolutional progression to CDKN2A/B homozygous deletion and NTRK fusion during recurrence: A case report|url=https://pubmed.ncbi.nlm.nih.gov/36265224|journal=Pathology, Research and Practice|volume=239|pages=154163|doi=10.1016/j.prp.2022.154163|issn=1618-0631|pmid=36265224}}</ref>
|-
|''NTRK2''
|''CDK5RAP2::NTRK2''
|N/A
|N/A
|Rare (observed in single case report)
|P, T
|No
|Single case report<ref>{{Cite journal|last=Kirishima|first=Mari|last2=Akahane|first2=Toshiaki|last3=Higa|first3=Nayuta|last4=Suzuki|first4=Shinsuke|last5=Ueno|first5=Shinichi|last6=Yonezawa|first6=Hajime|last7=Uchida|first7=Hiroyuki|last8=Hanaya|first8=Ryosuke|last9=Yoshimoto|first9=Koji|date=2022-11|title=IDH-mutant astrocytoma with an evolutional progression to CDKN2A/B homozygous deletion and NTRK fusion during recurrence: A case report|url=https://pubmed.ncbi.nlm.nih.gov/36265224|journal=Pathology, Research and Practice|volume=239|pages=154163|doi=10.1016/j.prp.2022.154163|issn=1618-0631|pmid=36265224}}</ref>
|-
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==Individual Region Genomic Gain/Loss/LOH==
<br />
{| class="wikitable sortable"
|-
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|9
|loss
|chr9:21,967,752-21,995,324
|''CDKN2A''
|P
|Yes  (WHO CNS5)
|Poorer prognosis<ref>{{Cite journal|last=Yang|first=Rui Ryan|last2=Shi|first2=Zhi-Feng|last3=Zhang|first3=Zhen-Yu|last4=Chan|first4=Aden Ka-Yin|last5=Aibaidula|first5=Abudumijiti|last6=Wang|first6=Wei-Wei|last7=Kwan|first7=Johnny Sheung Him|last8=Poon|first8=Wai Sang|last9=Chen|first9=Hong|date=2020-05|title=IDH mutant lower grade (WHO Grades II/III) astrocytomas can be stratified for risk by CDKN2A, CDK4 and PDGFRA copy number alterations|url=https://pubmed.ncbi.nlm.nih.gov/31733156|journal=Brain Pathology (Zurich, Switzerland)|volume=30|issue=3|pages=541–553|doi=10.1111/bpa.12801|issn=1750-3639|pmc=8018138|pmid=31733156}}</ref>
|-
|9
|loss
|chr9:22,002,903-22,009,313
|''CDKN2B''
|P
|Yes  (WHO CNS5)
|Poorer prognosis<ref>{{Cite journal|last=Lee|first=Kwanghoon|last2=Kim|first2=Seong-Ik|last3=Kim|first3=Eric Eunshik|last4=Shim|first4=Yu-Mi|last5=Won|first5=Jae-Kyung|last6=Park|first6=Chul-Kee|last7=Choi|first7=Seung Hong|last8=Yun|first8=Hongseok|last9=Lee|first9=Hyunju|date=2023-04-25|title=Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis|url=https://pubmed.ncbi.nlm.nih.gov/37185778|journal=Scientific Reports|volume=13|issue=1|pages=6761|doi=10.1038/s41598-023-32153-y|issn=2045-2322|pmc=10130138|pmid=37185778}}</ref>
|-
|12
|amp
|chr12:57,747,727-57,756,013
|''CDK4''
|P,T
|No
|Poorer prognosis<ref>{{Cite journal|last=Yang|first=Rui Ryan|last2=Shi|first2=Zhi-Feng|last3=Zhang|first3=Zhen-Yu|last4=Chan|first4=Aden Ka-Yin|last5=Aibaidula|first5=Abudumijiti|last6=Wang|first6=Wei-Wei|last7=Kwan|first7=Johnny Sheung Him|last8=Poon|first8=Wai Sang|last9=Chen|first9=Hong|date=2020-05|title=IDH mutant lower grade (WHO Grades II/III) astrocytomas can be stratified for risk by CDKN2A, CDK4 and PDGFRA copy number alterations|url=https://pubmed.ncbi.nlm.nih.gov/31733156|journal=Brain Pathology (Zurich, Switzerland)|volume=30|issue=3|pages=541–553|doi=10.1111/bpa.12801|issn=1750-3639|pmc=8018138|pmid=31733156}}</ref>
|-
|13
|loss
|chr13:48,303,744-48,599,436
|''RB1''
|P
|No
|<ref>{{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>
|-
|4
|amp
|chr4:54,229,280-54,298,245
|''PDGFRA''
|P
|No
|Poorer prognosis<ref>{{Cite journal|last=Yang|first=Rui Ryan|last2=Shi|first2=Zhi-Feng|last3=Zhang|first3=Zhen-Yu|last4=Chan|first4=Aden Ka-Yin|last5=Aibaidula|first5=Abudumijiti|last6=Wang|first6=Wei-Wei|last7=Kwan|first7=Johnny Sheung Him|last8=Poon|first8=Wai Sang|last9=Chen|first9=Hong|date=2020-05|title=IDH mutant lower grade (WHO Grades II/III) astrocytomas can be stratified for risk by CDKN2A, CDK4 and PDGFRA copy number alterations|url=https://pubmed.ncbi.nlm.nih.gov/31733156|journal=Brain Pathology (Zurich, Switzerland)|volume=30|issue=3|pages=541–553|doi=10.1111/bpa.12801|issn=1750-3639|pmc=8018138|pmid=31733156}}</ref>
|-
|2
|amp
|chr2:15,940,550-15,947,007
|''MYCN''
|P
|No
|Poorer  prognosis<ref>{{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><ref>{{Cite journal|last=Lee|first=Kwanghoon|last2=Kim|first2=Seong-Ik|last3=Kim|first3=Eric Eunshik|last4=Shim|first4=Yu-Mi|last5=Won|first5=Jae-Kyung|last6=Park|first6=Chul-Kee|last7=Choi|first7=Seung Hong|last8=Yun|first8=Hongseok|last9=Lee|first9=Hyunju|date=2023-04-25|title=Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis|url=https://pubmed.ncbi.nlm.nih.gov/37185778|journal=Scientific Reports|volume=13|issue=1|pages=6761|doi=10.1038/s41598-023-32153-y|issn=2045-2322|pmc=10130138|pmid=37185778}}</ref>
|-
|7
|amp
|chr7:116,672,196-116,798,377
|''MET''
|
|No
|<ref>{{Cite journal|last=Li|first=Kay Ka-Wai|last2=Shi|first2=Zhi-Feng|last3=Malta|first3=Tathiane M.|last4=Chan|first4=Aden Ka-Yin|last5=Cheng|first5=Shaz|last6=Kwan|first6=Johnny Sheung Him|last7=Yang|first7=Rui Ryan|last8=Poon|first8=Wai Sang|last9=Mao|first9=Ying|date=2019|title=Identification of subsets of IDH-mutant glioblastomas with distinct epigenetic and copy number alterations and stratified clinical risks|url=https://pubmed.ncbi.nlm.nih.gov/31667475|journal=Neuro-Oncology Advances|volume=1|issue=1|pages=vdz015|doi=10.1093/noajnl/vdz015|issn=2632-2498|pmc=6798792|pmid=31667475}}</ref>
|-
|10
|loss
|chr10:87863113-87971930
|''PTEN''
|P
|No
|<ref>{{Cite journal|last=Lee|first=Kwanghoon|last2=Kim|first2=Seong-Ik|last3=Kim|first3=Eric Eunshik|last4=Shim|first4=Yu-Mi|last5=Won|first5=Jae-Kyung|last6=Park|first6=Chul-Kee|last7=Choi|first7=Seung Hong|last8=Yun|first8=Hongseok|last9=Lee|first9=Hyunju|date=2023-04-25|title=Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis|url=https://pubmed.ncbi.nlm.nih.gov/37185778|journal=Scientific Reports|volume=13|issue=1|pages=6761|doi=10.1038/s41598-023-32153-y|issn=2045-2322|pmc=10130138|pmid=37185778}}</ref>
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==Characteristic Chromosomal or Other Global Mutational Patterns==
<br />
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Molecular Pathogenesis
!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|9p, 10q, 11p,  22q and 13q deletions
|N/A
|Rare
|P
|No
|Poor prognosis<ref>{{Cite journal|last=Tesileanu|first=C. Mircea S.|last2=Vallentgoed|first2=Wies R.|last3=French|first3=Pim J.|last4=van den Bent|first4=Martin J.|date=2022-11|title=Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review|url=https://pubmed.ncbi.nlm.nih.gov/36152406|journal=European Journal of Cancer (Oxford, England: 1990)|volume=175|pages=214–223|doi=10.1016/j.ejca.2022.08.016|issn=1879-0852|pmid=36152406}}</ref>
<br />
|-
|19q loss alone
|N/A
|Rare
|P
|No
|Better  outcome<ref>{{Cite journal|last=Mirchia|first=Kanish|last2=Richardson|first2=Timothy E.|date=2020-07-06|title=Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas|url=https://pubmed.ncbi.nlm.nih.gov/32640746|journal=Cancers|volume=12|issue=7|pages=1817|doi=10.3390/cancers12071817|issn=2072-6694|pmc=7408495|pmid=32640746}}</ref>
|-
|Gains chr 7  and chr 8q
|N/A
|Rare
|P
|No
|Poor  prognosis<ref>{{Cite journal|last=Tesileanu|first=C. Mircea S.|last2=Vallentgoed|first2=Wies R.|last3=French|first3=Pim J.|last4=van den Bent|first4=Martin J.|date=2022-11|title=Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review|url=https://pubmed.ncbi.nlm.nih.gov/36152406|journal=European Journal of Cancer (Oxford, England: 1990)|volume=175|pages=214–223|doi=10.1016/j.ejca.2022.08.016|issn=1879-0852|pmid=36152406}}</ref>
|-
|CNLOH chr17p
|N/A
|Rare
|P
|No
|Better  prognosis<ref>{{Cite journal|last=Tesileanu|first=C. Mircea S.|last2=Vallentgoed|first2=Wies R.|last3=French|first3=Pim J.|last4=van den Bent|first4=Martin J.|date=2022-11|title=Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review|url=https://pubmed.ncbi.nlm.nih.gov/36152406|journal=European Journal of Cancer (Oxford, England: 1990)|volume=175|pages=214–223|doi=10.1016/j.ejca.2022.08.016|issn=1879-0852|pmid=36152406}}</ref>
<br />
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==Gene Mutations (SNV/INDEL)==
<br />
{| class="wikitable sortable"
|-
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|''IDH1''
|Codon 132  activating mutations
|Oncogene
<br />
|Common
|D
|Yes (WHO CNS5)
|Essential  diagnostic criterion (WHO CNS 5)
|-
|''IDH2''
|Codon 172  activating mutations
|Oncogene
<br />
|Common
|D
|Yes (WHO CNS5)
|Essential  diagnostic criterion (WHO CNS 5)
|-
|''TP53''
|Variable  LOF mutations
|TSG
<br />
|Common
|D
|Yes (WHO CNS5)
|Desirable  diagnostic criterion (WHO CNS 5)
|-
|''ATRX''
|Variable  LOF mutations
|TSG
|Common
|D
|Yes (WHO CNS5)
|Desirable  diagnostic criterion (WHO CNS 5)
|-
|''TERT''
|Hotspot GOF mutation
|Oncogene
|Rare
|D
|Yes (WHO CNS5)
|Mutually exclusive with ATRX mutations<ref>{{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><ref>{{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><ref>{{Cite journal|last=Killela|first=Patrick J.|last2=Reitman|first2=Zachary J.|last3=Jiao|first3=Yuchen|last4=Bettegowda|first4=Chetan|last5=Agrawal|first5=Nishant|last6=Diaz|first6=Luis A.|last7=Friedman|first7=Allan H.|last8=Friedman|first8=Henry|last9=Gallia|first9=Gary L.|date=2013-04-09|title=TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal|url=https://pubmed.ncbi.nlm.nih.gov/23530248|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=110|issue=15|pages=6021–6026|doi=10.1073/pnas.1303607110|issn=1091-6490|pmc=3625331|pmid=23530248}}</ref>
|-
|''MET''
|Splicing variant
|Oncogene
|Rare
|P
|No
|Poorer prognosis<ref>{{Cite journal|last=Liu|first=Lingyu|last2=Zhang|first2=Ke-Nan|last3=Zhao|first3=Zheng|last4=Li|first4=Guanzhang|last5=Chai|first5=Rui-Chao|last6=Li|first6=Zhuoqun|last7=Liu|first7=Xing|last8=Chen|first8=Jing|last9=Jiang|first9=Tao|date=2024-05|title=MET fusions and splicing variants is a strong adverse prognostic factor in astrocytoma, isocitrate dehydrogenase mutant|url=https://pubmed.ncbi.nlm.nih.gov/37530224|journal=Brain Pathology (Zurich, Switzerland)|volume=34|issue=3|pages=e13198|doi=10.1111/bpa.13198|issn=1750-3639|pmc=11007006|pmid=37530224}}</ref>
|-
|''PIK3R1''
|Variable  LOF mutations
|TSG
|Rare
|P
|No
|Poorer prognosis<ref>{{Cite journal|last=Aoki|first=Kosuke|last2=Nakamura|first2=Hideo|last3=Suzuki|first3=Hiromichi|last4=Matsuo|first4=Keitaro|last5=Kataoka|first5=Keisuke|last6=Shimamura|first6=Teppei|last7=Motomura|first7=Kazuya|last8=Ohka|first8=Fumiharu|last9=Shiina|first9=Satoshi|date=2018-01-10|title=Prognostic relevance of genetic alterations in diffuse lower-grade gliomas|url=https://pubmed.ncbi.nlm.nih.gov/29016839|journal=Neuro-Oncology|volume=20|issue=1|pages=66–77|doi=10.1093/neuonc/nox132|issn=1523-5866|pmc=5761527|pmid=29016839}}</ref><ref>{{Cite journal|last=Wong|first=Queenie Hoi-Wing|last2=Li|first2=Kay Ka-Wai|last3=Wang|first3=Wei-Wei|last4=Malta|first4=Tathiane M.|last5=Noushmehr|first5=Houtan|last6=Grabovska|first6=Yura|last7=Jones|first7=Chris|last8=Chan|first8=Aden Ka-Yin|last9=Kwan|first9=Johnny Sheung-Him|date=2021-07|title=Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas|url=https://pubmed.ncbi.nlm.nih.gov/33692446|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=34|issue=7|pages=1245–1260|doi=10.1038/s41379-021-00778-x|issn=1530-0285|pmid=33692446}}</ref>
|-
|''PIK3CA''
|Exon 10,  exon 21 activating mutations
|Oncogene
|Rare
|P
|No
|Poorer prognosis<ref>{{Cite journal|last=Wong|first=Queenie Hoi-Wing|last2=Li|first2=Kay Ka-Wai|last3=Wang|first3=Wei-Wei|last4=Malta|first4=Tathiane M.|last5=Noushmehr|first5=Houtan|last6=Grabovska|first6=Yura|last7=Jones|first7=Chris|last8=Chan|first8=Aden Ka-Yin|last9=Kwan|first9=Johnny Sheung-Him|date=2021-07|title=Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas|url=https://pubmed.ncbi.nlm.nih.gov/33692446|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=34|issue=7|pages=1245–1260|doi=10.1038/s41379-021-00778-x|issn=1530-0285|pmid=33692446}}</ref><ref>{{Cite journal|last=Aoki|first=Kosuke|last2=Nakamura|first2=Hideo|last3=Suzuki|first3=Hiromichi|last4=Matsuo|first4=Keitaro|last5=Kataoka|first5=Keisuke|last6=Shimamura|first6=Teppei|last7=Motomura|first7=Kazuya|last8=Ohka|first8=Fumiharu|last9=Shiina|first9=Satoshi|date=2018-01-10|title=Prognostic relevance of genetic alterations in diffuse lower-grade gliomas|url=https://pubmed.ncbi.nlm.nih.gov/29016839|journal=Neuro-Oncology|volume=20|issue=1|pages=66–77|doi=10.1093/neuonc/nox132|issn=1523-5866|pmc=5761527|pmid=29016839}}</ref>
|-
|''TTN''
|Activating mutations
|Oncogene
|Rare
|
|No
|<ref>{{Cite journal|last=Zhao|first=Binghao|last2=Xia|first2=Yu|last3=Yang|first3=Fengchun|last4=Wang|first4=Yaning|last5=Wang|first5=Yuekun|last6=Wang|first6=Yadong|last7=Dai|first7=Congxin|last8=Wang|first8=Yu|last9=Ma|first9=Wenbin|date=2022-03-14|title=Molecular landscape of IDH-mutant astrocytoma and oligodendroglioma grade 2 indicate tumor purity as an underlying genomic factor|url=https://pubmed.ncbi.nlm.nih.gov/35287567|journal=Molecular Medicine (Cambridge, Mass.)|volume=28|issue=1|pages=34|doi=10.1186/s10020-022-00454-z|issn=1528-3658|pmc=8919570|pmid=35287567}}</ref>
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
==Epigenomic Alterations==
''MGMT'' promoter methylation (73%)<ref>{{Cite journal|last=Nakamura|first=M.|last2=Watanabe|first2=T.|last3=Yonekawa|first3=Y.|last4=Kleihues|first4=P.|last5=Ohgaki|first5=H.|date=2001-10|title=Promoter methylation of the DNA repair gene MGMT in astrocytomas is frequently associated with G:C --> A:T mutations of the TP53 tumor suppressor gene|url=https://pubmed.ncbi.nlm.nih.gov/11577014|journal=Carcinogenesis|volume=22|issue=10|pages=1715–1719|doi=10.1093/carcin/22.10.1715|issn=0143-3334|pmid=11577014}}</ref> <ref>{{Cite journal|last=Turcan|first=Sevin|last2=Rohle|first2=Daniel|last3=Goenka|first3=Anuj|last4=Walsh|first4=Logan A.|last5=Fang|first5=Fang|last6=Yilmaz|first6=Emrullah|last7=Campos|first7=Carl|last8=Fabius|first8=Armida W. M.|last9=Lu|first9=Chao|date=2012-02-15|title=IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype|url=https://pubmed.ncbi.nlm.nih.gov/22343889|journal=Nature|volume=483|issue=7390|pages=479–483|doi=10.1038/nature10866|issn=1476-4687|pmc=3351699|pmid=22343889}}</ref>
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
{| class="wikitable sortable"
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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|Homozygous deletion of ''CDKN2A'', ''CDKN2B'',  ''RB1'', and ''CDK4''
|RB pathway
|Increased cell growth and proliferation  Negatively correlated with overall survival<ref>{{Cite journal|last=Tesileanu|first=C. Mircea S.|last2=Vallentgoed|first2=Wies R.|last3=French|first3=Pim J.|last4=van den Bent|first4=Martin J.|date=2022-11|title=Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review|url=https://pubmed.ncbi.nlm.nih.gov/36152406|journal=European Journal of Cancer (Oxford, England: 1990)|volume=175|pages=214–223|doi=10.1016/j.ejca.2022.08.016|issn=1879-0852|pmid=36152406}}</ref>
|-
|Amp of ''PDGFRA'' and activating  mutations in PI3K genes
|RTK-PI3K-mTOR
|Increased activation induces cell cycle  progression<ref>{{Cite journal|last=Tesileanu|first=C. Mircea S.|last2=Vallentgoed|first2=Wies R.|last3=French|first3=Pim J.|last4=van den Bent|first4=Martin J.|date=2022-11|title=Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review|url=https://pubmed.ncbi.nlm.nih.gov/36152406|journal=European Journal of Cancer (Oxford, England: 1990)|volume=175|pages=214–223|doi=10.1016/j.ejca.2022.08.016|issn=1879-0852|pmid=36152406}}</ref>  
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==Genetic Diagnostic Testing Methods==
·      Initial diagnostic workup is performed by using routine immunohistochemical panel which involves IDH1 R132H, p53 and ATRX IHC
 
·      In case of negative and indeterminate IHC results, sequencing need to be performed for ''IDH1'' codon 132 and ''IDH2'' codon 172, to detect non-canonical (non-R132H) ''IDH1/2'' mutations.
 
==Familial Forms==
·      Generally sporadic but low frequency SNP at 8q24.21 associated with increased risk<ref>{{Cite journal|last=Batchelor|first=Tracy T.|last2=Walsh|first2=Kyle M.|date=2023-04-06|title=Understanding the Genetic Risk of IDH-Mutant Glioma|url=https://pubmed.ncbi.nlm.nih.gov/37018498|journal=The New England Journal of Medicine|volume=388|issue=14|pages=1332–1334|doi=10.1056/NEJMcibr2213112|issn=1533-4406|pmid=37018498}}</ref>
 
·      Variants at 8q24.21 (''CCDC'' locus), ''PHLDB1, AKT3, IDH1, D2HGDH''<ref>{{Cite journal|last=Batchelor|first=Tracy T.|last2=Walsh|first2=Kyle M.|date=2023-04-06|title=Understanding the Genetic Risk of IDH-Mutant Glioma|url=https://pubmed.ncbi.nlm.nih.gov/37018498|journal=The New England Journal of Medicine|volume=388|issue=14|pages=1332–1334|doi=10.1056/NEJMcibr2213112|issn=1533-4406|pmid=37018498}}</ref>
 
·      Li-Fraumeni syndrome characterized by germline ''TP53'' mutations<ref>{{Cite journal|last=Watanabe|first=Takuya|last2=Vital|first2=Anne|last3=Nobusawa|first3=Sumihito|last4=Kleihues|first4=Paul|last5=Ohgaki|first5=Hiroko|date=2009-06|title=Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19340432|journal=Acta Neuropathologica|volume=117|issue=6|pages=653–656|doi=10.1007/s00401-009-0528-x|issn=1432-0533|pmid=19340432}}</ref>
 
·      IDH1R132C mutations in tumors with germline ''TP53'' mutation<ref>{{Cite journal|last=Watanabe|first=Takuya|last2=Vital|first2=Anne|last3=Nobusawa|first3=Sumihito|last4=Kleihues|first4=Paul|last5=Ohgaki|first5=Hiroko|date=2009-06|title=Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19340432|journal=Acta Neuropathologica|volume=117|issue=6|pages=653–656|doi=10.1007/s00401-009-0528-x|issn=1432-0533|pmid=19340432}}</ref>
 
·      Patients with inherited Ollier disease<ref>{{Cite journal|last=Corvino|first=Sergio|last2=Mariniello|first2=Giuseppe|last3=Corazzelli|first3=Giuseppe|last4=Franca|first4=Raduan Ahmed|last5=Del Basso De Caro|first5=Marialaura|last6=Della Monica|first6=Rosa|last7=Chiariotti|first7=Lorenzo|last8=Maiuri|first8=Francesco|date=2022-07-16|title=Brain Gliomas and Ollier Disease: Molecular Findings as Predictive Risk Factors?|url=https://pubmed.ncbi.nlm.nih.gov/35884525|journal=Cancers|volume=14|issue=14|pages=3464|doi=10.3390/cancers14143464|issn=2072-6694|pmc=9324397|pmid=35884525}}</ref>
 
·      Germline mutations in mismatch repair genes (pediatric and adults)<ref>{{Cite journal|last=Richardson|first=Timothy E.|last2=Yokoda|first2=Raquel T.|last3=Rashidipour|first3=Omid|last4=Vij|first4=Meenakshi|last5=Snuderl|first5=Matija|last6=Brem|first6=Steven|last7=Hatanpaa|first7=Kimmo J.|last8=McBrayer|first8=Samuel K.|last9=Abdullah|first9=Kalil G.|date=2023|title=Mismatch repair protein mutations in isocitrate dehydrogenase (IDH)-mutant astrocytoma and IDH-wild-type glioblastoma|url=https://pubmed.ncbi.nlm.nih.gov/37554222|journal=Neuro-Oncology Advances|volume=5|issue=1|pages=vdad085|doi=10.1093/noajnl/vdad085|issn=2632-2498|pmc=10406418|pmid=37554222}}</ref>
 
==References==
<br />
[[Category:CNS5]]
[[Category:DISEASE]]
[[Category:Diseases A]]
<references />
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
 
Prior Author(s):
<nowiki>*</nowiki>''Citation of this Page'': “Astrocytoma, IDH-mutant”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/CNS5:Astrocytoma, IDH-mutant</nowiki>.
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