CNS5:Astrocytoma, IDH-mutant: Difference between revisions

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==Primary Author(s)*==
{{DISPLAYTITLE:Astrocytoma, IDH-mutant}}


Put your text here
[[CNS5:Table_of_Contents|Central Nervous System Tumours (WHO Classification, 5th ed.)]]


__TOC__
{{Under Construction}}
==Primary Author(s)*==
Meenakshi Mehrotra, PhD, Mount Sinai Health System, New York
==WHO Classification of Disease==


==Cancer Category/Type==
{| class="wikitable"
 
!Structure
Put your text here
!Disease
 
|-
==Cancer Sub-Classification / Subtype==
|Book
 
|Central Nervous System Tumours (5th ed.)
Put your text here
|-
 
|Category
==Definition / Description of Disease==
|Gliomas, glioneuronal tumours, and neuronal tumours
 
|-
Put your text here
|Family
 
|Gliomas, glioneuronal tumours, and neuronal tumours
==Synonyms / Terminology==
|-
 
|Type
Put your text here
|Adult-type diffuse gliomas
 
|-
==Epidemiology / Prevalence==
|Subtype(s)
 
|Astrocytoma, IDH-mutant
Put your text here
|}


==Clinical Features==
==Related Terminology==


Put your text here and fill in the table
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
|Acceptable
 
|N/A
EXAMPLE B-symptoms (weight loss, fever, night sweats)
 
EXAMPLE Fatigue
 
EXAMPLE Lymphadenopathy (uncommon)
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|EXAMPLE Cytopenias
|Diffuse astrocytoma, IDH-mutant; anaplastic astrocytoma, IDH-mutant; glioblastoma, IDH-mutant; low-grade astrocytoma; lower-grade astrocytoma; high-grade astrocytoma; infiltrating astrocytoma; diffuse glioma
 
EXAMPLE Lymphocytosis (low level)
|}
|}


==Sites of Involvement==
==Gene Rearrangements==
 
<br />
Put your text here
 
==Morphologic Features==
 
Put your text here
 
==Immunophenotype==
 
Put your text here and fill in the table
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!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
|-
|-
|Positive (universal)||EXAMPLE CD1
|''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>
|-
|-
|Positive (subset)||EXAMPLE CD2
|''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>
|-
|-
|Negative (universal)||EXAMPLE CD3
|''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>
|-
|
|
|
|
|
|
|
|
|-
|-
|Negative (subset)||EXAMPLE CD4
|
|
|
|
|
|
|
|
|}
|}
 
==Individual Region Genomic Gain/Loss/LOH==
==Chromosomal Rearrangements (Gene Fusions)==
<br />
 
Put your text here and fill in the table
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Prognostic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Therapeutic Significance (Yes, No or Unknown)
!Clinical Relevance Details/Other Notes
!Notes
|-
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
|9
EXAMPLE 30% (add reference)
|loss
|Yes
|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
|No
|Yes
|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>
|EXAMPLE
 
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}
==Individual Region Genomic Gain/Loss/LOH==
 
Put your text here and fill in the table
 
{| class="wikitable sortable"
|-
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
|13
!Diagnostic Significance (Yes, No or Unknown)
|loss
!Prognostic Significance (Yes, No or Unknown)
|chr13:48,303,744-48,599,436
!Therapeutic Significance (Yes, No or Unknown)
|''RB1''
!Notes
|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>
|-
|-
|EXAMPLE
|4
 
|amp
7
|chr4:54,229,280-54,298,245
|EXAMPLE Loss
|''PDGFRA''
|EXAMPLE
|P
 
chr7:1- 159,335,973 [hg38]
|EXAMPLE
 
chr7
|Yes
|Yes
|No
|No
|EXAMPLE
|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>
 
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|-
|EXAMPLE
|2
 
|amp
8
|chr2:15,940,550-15,947,007
|EXAMPLE Gain
|''MYCN''
|EXAMPLE
|P
 
chr8:1-145,138,636 [hg38]
|EXAMPLE
 
chr8
|No
|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
|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
|No
|EXAMPLE
|<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>
 
|-
Common recurrent secondary finding for t(8;21) (add reference).
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==Characteristic Chromosomal Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
 
<br />
Put your text here
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
!Prevalence -
!Therapeutic Significance (Yes, No or Unknown)
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Notes
!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>
|-
|-
|EXAMPLE
|Gains chr 7  and chr 8q
 
|N/A
Co-deletion of 1p and 18q
|Rare
|Yes
|P
|No
|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
|No
|EXAMPLE:
|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 />
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|-
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|}
==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
 
<br />
Put your text here and fill in the table
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
!'''Diagnostic Significance (Yes, No or Unknown)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Prognostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Therapeutic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Notes
!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>
|-
|-
|EXAMPLE: TP53; Variable LOF mutations
|''MET''
 
|Splicing variant
EXAMPLE:
|Oncogene
 
|Rare
EGFR; Exon 20 mutations
|P
 
|No
EXAMPLE: BRAF; Activating mutations
|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>
|EXAMPLE: TSG
|-
|EXAMPLE: 20% (COSMIC)
|''PIK3R1''
 
|Variable LOF mutations
EXAMPLE: 30% (add Reference)
|TSG
|EXAMPLE: IDH1 R123H
|Rare
|EXAMPLE: EGFR amplification
|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>
|EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
|}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.
<br />
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
 
==Epigenomic Alterations==
==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>
Put your text here
 
==Genes and Main Pathways Involved==
==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>
Put your text here and fill in the table
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|Homozygous deletion of ''CDKN2A'', ''CDKN2B'',  ''RB1'', and ''CDK4''
|EXAMPLE: MAPK signaling
|RB pathway
|EXAMPLE: Increased cell growth and proliferation
|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>  
|-
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|
|EXAMPLE: Cell cycle regulation
|
|EXAMPLE: Unregulated cell division
|
|-
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|
|EXAMPLE:  Histone modification, chromatin remodeling
|
|EXAMPLE:  Abnormal gene expression program
|
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
·      Initial diagnostic workup is performed by using routine immunohistochemical panel which involves IDH1 R132H, p53 and ATRX IHC


Put your text here
·      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==
==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>


Put your text here
·      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>
==Additional Information==
==Additional Information==
Put your text here
Put your text here
==Links==
==Links==
 
Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
Put your text placeholder here (use "Link" icon at top of page)
 
==References==
==References==
<br />
[[Category:CNS5]]
[[Category:DISEASE]]
[[Category:Diseases A]]
<references />
<references />
(use "Cite" icon at top of page)
==Notes==
===EXAMPLE Book===
<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.


#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.
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>.
==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 CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

Latest revision as of 13:39, 21 April 2026


Central Nervous System Tumours (WHO Classification, 5th ed.)

Primary Author(s)*

Meenakshi Mehrotra, PhD, Mount Sinai Health System, New York

WHO Classification of Disease

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

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


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[1][2]
NTRK2 GOLGA1::NTRK2 N/A N/A Rare (observed in single case report) P, T No Single case report[3]
NTRK2 CDK5RAP2::NTRK2 N/A N/A Rare (observed in single case report) P, T No Single case report[4]

Individual Region Genomic Gain/Loss/LOH


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[5]
9 loss chr9:22,002,903-22,009,313 CDKN2B P Yes  (WHO CNS5) Poorer prognosis[6]
12 amp chr12:57,747,727-57,756,013 CDK4 P,T No Poorer prognosis[7]
13 loss chr13:48,303,744-48,599,436 RB1 P No [8]
4 amp chr4:54,229,280-54,298,245 PDGFRA P No Poorer prognosis[9]
2 amp chr2:15,940,550-15,947,007 MYCN P No Poorer prognosis[10][11]
7 amp chr7:116,672,196-116,798,377 MET No [12]
10 loss chr10:87863113-87971930 PTEN P No [13]

Characteristic Chromosomal or Other Global Mutational Patterns


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[14]


19q loss alone N/A Rare P No Better outcome[15]
Gains chr 7 and chr 8q N/A Rare P No Poor prognosis[16]
CNLOH chr17p N/A Rare P No Better prognosis[17]


Gene Mutations (SNV/INDEL)


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


Common D Yes (WHO CNS5) Essential diagnostic criterion (WHO CNS 5)
IDH2 Codon 172 activating mutations Oncogene


Common D Yes (WHO CNS5) Essential diagnostic criterion (WHO CNS 5)
TP53 Variable LOF mutations TSG


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[18][19][20]
MET Splicing variant Oncogene Rare P No Poorer prognosis[21]
PIK3R1 Variable LOF mutations TSG Rare P No Poorer prognosis[22][23]
PIK3CA Exon 10, exon 21 activating mutations Oncogene Rare P No Poorer prognosis[24][25]
TTN Activating mutations Oncogene Rare No [26]

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, 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%)[27] [28]

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete the table.)

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[29]
Amp of PDGFRA and activating mutations in PI3K genes RTK-PI3K-mTOR Increased activation induces cell cycle progression[30]  

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[31]

·      Variants at 8q24.21 (CCDC locus), PHLDB1, AKT3, IDH1, D2HGDH[32]

·      Li-Fraumeni syndrome characterized by germline TP53 mutations[33]

·      IDH1R132C mutations in tumors with germline TP53 mutation[34]

·      Patients with inherited Ollier disease[35]

·      Germline mutations in mismatch repair genes (pediatric and adults)[36]

Additional Information

Put your text here

Links

Put a link here or anywhere appropriate in this page (Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)

References


  1. ↑ Liu, Lingyu; Zhang, Ke-Nan; Zhao, Zheng; Li, Guanzhang; Chai, Rui-Chao; Li, Zhuoqun; Liu, Xing; Chen, Jing; Jiang, Tao (2024-05). "MET fusions and splicing variants is a strong adverse prognostic factor in astrocytoma, isocitrate dehydrogenase mutant". Brain Pathology (Zurich, Switzerland). 34 (3): e13198. doi:10.1111/bpa.13198. ISSN 1750-3639. PMC 11007006. PMID 37530224. {{cite journal}}: Check date values in: |date= (help)CS1 maint: article number as page number (link)
  2. ↑ Wong, Queenie Hoi-Wing; Li, Kay Ka-Wai; Wang, Wei-Wei; Malta, Tathiane M.; Noushmehr, Houtan; Grabovska, Yura; Jones, Chris; Chan, Aden Ka-Yin; Kwan, Johnny Sheung-Him (2021-07). "Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 34 (7): 1245–1260. doi:10.1038/s41379-021-00778-x. ISSN 1530-0285. PMID 33692446. {{cite journal}}: Check date values in: |date= (help)
  3. ↑ Kirishima, Mari; Akahane, Toshiaki; Higa, Nayuta; Suzuki, Shinsuke; Ueno, Shinichi; Yonezawa, Hajime; Uchida, Hiroyuki; Hanaya, Ryosuke; Yoshimoto, Koji (2022-11). "IDH-mutant astrocytoma with an evolutional progression to CDKN2A/B homozygous deletion and NTRK fusion during recurrence: A case report". Pathology, Research and Practice. 239: 154163. doi:10.1016/j.prp.2022.154163. ISSN 1618-0631. PMID 36265224. {{cite journal}}: Check date values in: |date= (help)CS1 maint: article number as page number (link)
  4. ↑ Kirishima, Mari; Akahane, Toshiaki; Higa, Nayuta; Suzuki, Shinsuke; Ueno, Shinichi; Yonezawa, Hajime; Uchida, Hiroyuki; Hanaya, Ryosuke; Yoshimoto, Koji (2022-11). "IDH-mutant astrocytoma with an evolutional progression to CDKN2A/B homozygous deletion and NTRK fusion during recurrence: A case report". Pathology, Research and Practice. 239: 154163. doi:10.1016/j.prp.2022.154163. ISSN 1618-0631. PMID 36265224. {{cite journal}}: Check date values in: |date= (help)CS1 maint: article number as page number (link)
  5. ↑ Yang, Rui Ryan; Shi, Zhi-Feng; Zhang, Zhen-Yu; Chan, Aden Ka-Yin; Aibaidula, Abudumijiti; Wang, Wei-Wei; Kwan, Johnny Sheung Him; Poon, Wai Sang; Chen, Hong (2020-05). "IDH mutant lower grade (WHO Grades II/III) astrocytomas can be stratified for risk by CDKN2A, CDK4 and PDGFRA copy number alterations". Brain Pathology (Zurich, Switzerland). 30 (3): 541–553. doi:10.1111/bpa.12801. ISSN 1750-3639. PMC 8018138. PMID 31733156. {{cite journal}}: Check date values in: |date= (help)
  6. ↑ Lee, Kwanghoon; Kim, Seong-Ik; Kim, Eric Eunshik; Shim, Yu-Mi; Won, Jae-Kyung; Park, Chul-Kee; Choi, Seung Hong; Yun, Hongseok; Lee, Hyunju (2023-04-25). "Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis". Scientific Reports. 13 (1): 6761. doi:10.1038/s41598-023-32153-y. ISSN 2045-2322. PMC 10130138. PMID 37185778.
  7. ↑ Yang, Rui Ryan; Shi, Zhi-Feng; Zhang, Zhen-Yu; Chan, Aden Ka-Yin; Aibaidula, Abudumijiti; Wang, Wei-Wei; Kwan, Johnny Sheung Him; Poon, Wai Sang; Chen, Hong (2020-05). "IDH mutant lower grade (WHO Grades II/III) astrocytomas can be stratified for risk by CDKN2A, CDK4 and PDGFRA copy number alterations". Brain Pathology (Zurich, Switzerland). 30 (3): 541–553. doi:10.1111/bpa.12801. ISSN 1750-3639. PMC 8018138. PMID 31733156. {{cite journal}}: Check date values in: |date= (help)
  8. ↑ Shirahata, Mitsuaki; Ono, Takahiro; Stichel, Damian; Schrimpf, Daniel; Reuss, David E.; Sahm, Felix; Koelsche, Christian; Wefers, Annika; Reinhardt, Annekathrin (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. {{cite journal}}: Check date values in: |date= (help)
  9. ↑ Yang, Rui Ryan; Shi, Zhi-Feng; Zhang, Zhen-Yu; Chan, Aden Ka-Yin; Aibaidula, Abudumijiti; Wang, Wei-Wei; Kwan, Johnny Sheung Him; Poon, Wai Sang; Chen, Hong (2020-05). "IDH mutant lower grade (WHO Grades II/III) astrocytomas can be stratified for risk by CDKN2A, CDK4 and PDGFRA copy number alterations". Brain Pathology (Zurich, Switzerland). 30 (3): 541–553. doi:10.1111/bpa.12801. ISSN 1750-3639. PMC 8018138. PMID 31733156. {{cite journal}}: Check date values in: |date= (help)
  10. ↑ Shirahata, Mitsuaki; Ono, Takahiro; Stichel, Damian; Schrimpf, Daniel; Reuss, David E.; Sahm, Felix; Koelsche, Christian; Wefers, Annika; Reinhardt, Annekathrin (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. {{cite journal}}: Check date values in: |date= (help)
  11. ↑ Lee, Kwanghoon; Kim, Seong-Ik; Kim, Eric Eunshik; Shim, Yu-Mi; Won, Jae-Kyung; Park, Chul-Kee; Choi, Seung Hong; Yun, Hongseok; Lee, Hyunju (2023-04-25). "Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis". Scientific Reports. 13 (1): 6761. doi:10.1038/s41598-023-32153-y. ISSN 2045-2322. PMC 10130138. PMID 37185778.
  12. ↑ Li, Kay Ka-Wai; Shi, Zhi-Feng; Malta, Tathiane M.; Chan, Aden Ka-Yin; Cheng, Shaz; Kwan, Johnny Sheung Him; Yang, Rui Ryan; Poon, Wai Sang; Mao, Ying (2019). "Identification of subsets of IDH-mutant glioblastomas with distinct epigenetic and copy number alterations and stratified clinical risks". Neuro-Oncology Advances. 1 (1): vdz015. doi:10.1093/noajnl/vdz015. ISSN 2632-2498. PMC 6798792. PMID 31667475.{{cite journal}}: CS1 maint: article number as page number (link)
  13. ↑ Lee, Kwanghoon; Kim, Seong-Ik; Kim, Eric Eunshik; Shim, Yu-Mi; Won, Jae-Kyung; Park, Chul-Kee; Choi, Seung Hong; Yun, Hongseok; Lee, Hyunju (2023-04-25). "Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis". Scientific Reports. 13 (1): 6761. doi:10.1038/s41598-023-32153-y. ISSN 2045-2322. PMC 10130138. PMID 37185778.
  14. ↑ Tesileanu, C. Mircea S.; Vallentgoed, Wies R.; French, Pim J.; van den Bent, Martin J. (2022-11). "Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review". European Journal of Cancer (Oxford, England: 1990). 175: 214–223. doi:10.1016/j.ejca.2022.08.016. ISSN 1879-0852. PMID 36152406. {{cite journal}}: Check date values in: |date= (help)
  15. ↑ Mirchia, Kanish; Richardson, Timothy E. (2020-07-06). "Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas". Cancers. 12 (7): 1817. doi:10.3390/cancers12071817. ISSN 2072-6694. PMC 7408495. PMID 32640746.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  16. ↑ Tesileanu, C. Mircea S.; Vallentgoed, Wies R.; French, Pim J.; van den Bent, Martin J. (2022-11). "Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review". European Journal of Cancer (Oxford, England: 1990). 175: 214–223. doi:10.1016/j.ejca.2022.08.016. ISSN 1879-0852. PMID 36152406. {{cite journal}}: Check date values in: |date= (help)
  17. ↑ Tesileanu, C. Mircea S.; Vallentgoed, Wies R.; French, Pim J.; van den Bent, Martin J. (2022-11). "Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review". European Journal of Cancer (Oxford, England: 1990). 175: 214–223. doi:10.1016/j.ejca.2022.08.016. ISSN 1879-0852. PMID 36152406. {{cite journal}}: Check date values in: |date= (help)
  18. ↑ Cancer Genome Atlas Research Network; Brat, Daniel J.; Verhaak, Roel G. W.; Aldape, Kenneth D.; Yung, W. K. Alfred; Salama, Sofie R.; Cooper, Lee A. D.; Rheinbay, Esther; Miller, C. Ryan (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.
  19. ↑ Eckel-Passow, Jeanette E.; Lachance, Daniel H.; Molinaro, Annette M.; Walsh, Kyle M.; Decker, Paul A.; Sicotte, Hugues; Pekmezci, Melike; Rice, Terri; Kosel, Matt L. (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.
  20. ↑ Killela, Patrick J.; Reitman, Zachary J.; Jiao, Yuchen; Bettegowda, Chetan; Agrawal, Nishant; Diaz, Luis A.; Friedman, Allan H.; Friedman, Henry; Gallia, Gary L. (2013-04-09). "TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal". Proceedings of the National Academy of Sciences of the United States of America. 110 (15): 6021–6026. doi:10.1073/pnas.1303607110. ISSN 1091-6490. PMC 3625331. PMID 23530248.
  21. ↑ Liu, Lingyu; Zhang, Ke-Nan; Zhao, Zheng; Li, Guanzhang; Chai, Rui-Chao; Li, Zhuoqun; Liu, Xing; Chen, Jing; Jiang, Tao (2024-05). "MET fusions and splicing variants is a strong adverse prognostic factor in astrocytoma, isocitrate dehydrogenase mutant". Brain Pathology (Zurich, Switzerland). 34 (3): e13198. doi:10.1111/bpa.13198. ISSN 1750-3639. PMC 11007006. PMID 37530224. {{cite journal}}: Check date values in: |date= (help)CS1 maint: article number as page number (link)
  22. ↑ Aoki, Kosuke; Nakamura, Hideo; Suzuki, Hiromichi; Matsuo, Keitaro; Kataoka, Keisuke; Shimamura, Teppei; Motomura, Kazuya; Ohka, Fumiharu; Shiina, Satoshi (2018-01-10). "Prognostic relevance of genetic alterations in diffuse lower-grade gliomas". Neuro-Oncology. 20 (1): 66–77. doi:10.1093/neuonc/nox132. ISSN 1523-5866. PMC 5761527. PMID 29016839.
  23. ↑ Wong, Queenie Hoi-Wing; Li, Kay Ka-Wai; Wang, Wei-Wei; Malta, Tathiane M.; Noushmehr, Houtan; Grabovska, Yura; Jones, Chris; Chan, Aden Ka-Yin; Kwan, Johnny Sheung-Him (2021-07). "Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 34 (7): 1245–1260. doi:10.1038/s41379-021-00778-x. ISSN 1530-0285. PMID 33692446. {{cite journal}}: Check date values in: |date= (help)
  24. ↑ Wong, Queenie Hoi-Wing; Li, Kay Ka-Wai; Wang, Wei-Wei; Malta, Tathiane M.; Noushmehr, Houtan; Grabovska, Yura; Jones, Chris; Chan, Aden Ka-Yin; Kwan, Johnny Sheung-Him (2021-07). "Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 34 (7): 1245–1260. doi:10.1038/s41379-021-00778-x. ISSN 1530-0285. PMID 33692446. {{cite journal}}: Check date values in: |date= (help)
  25. ↑ Aoki, Kosuke; Nakamura, Hideo; Suzuki, Hiromichi; Matsuo, Keitaro; Kataoka, Keisuke; Shimamura, Teppei; Motomura, Kazuya; Ohka, Fumiharu; Shiina, Satoshi (2018-01-10). "Prognostic relevance of genetic alterations in diffuse lower-grade gliomas". Neuro-Oncology. 20 (1): 66–77. doi:10.1093/neuonc/nox132. ISSN 1523-5866. PMC 5761527. PMID 29016839.
  26. ↑ Zhao, Binghao; Xia, Yu; Yang, Fengchun; Wang, Yaning; Wang, Yuekun; Wang, Yadong; Dai, Congxin; Wang, Yu; Ma, Wenbin (2022-03-14). "Molecular landscape of IDH-mutant astrocytoma and oligodendroglioma grade 2 indicate tumor purity as an underlying genomic factor". Molecular Medicine (Cambridge, Mass.). 28 (1): 34. doi:10.1186/s10020-022-00454-z. ISSN 1528-3658. PMC 8919570. PMID 35287567.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  27. ↑ Nakamura, M.; Watanabe, T.; Yonekawa, Y.; Kleihues, P.; Ohgaki, H. (2001-10). "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". Carcinogenesis. 22 (10): 1715–1719. doi:10.1093/carcin/22.10.1715. ISSN 0143-3334. PMID 11577014. {{cite journal}}: Check date values in: |date= (help)
  28. ↑ Turcan, Sevin; Rohle, Daniel; Goenka, Anuj; Walsh, Logan A.; Fang, Fang; Yilmaz, Emrullah; Campos, Carl; Fabius, Armida W. M.; Lu, Chao (2012-02-15). "IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype". Nature. 483 (7390): 479–483. doi:10.1038/nature10866. ISSN 1476-4687. PMC 3351699. PMID 22343889.
  29. ↑ Tesileanu, C. Mircea S.; Vallentgoed, Wies R.; French, Pim J.; van den Bent, Martin J. (2022-11). "Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review". European Journal of Cancer (Oxford, England: 1990). 175: 214–223. doi:10.1016/j.ejca.2022.08.016. ISSN 1879-0852. PMID 36152406. {{cite journal}}: Check date values in: |date= (help)
  30. ↑ Tesileanu, C. Mircea S.; Vallentgoed, Wies R.; French, Pim J.; van den Bent, Martin J. (2022-11). "Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review". European Journal of Cancer (Oxford, England: 1990). 175: 214–223. doi:10.1016/j.ejca.2022.08.016. ISSN 1879-0852. PMID 36152406. {{cite journal}}: Check date values in: |date= (help)
  31. ↑ Batchelor, Tracy T.; Walsh, Kyle M. (2023-04-06). "Understanding the Genetic Risk of IDH-Mutant Glioma". The New England Journal of Medicine. 388 (14): 1332–1334. doi:10.1056/NEJMcibr2213112. ISSN 1533-4406. PMID 37018498.
  32. ↑ Batchelor, Tracy T.; Walsh, Kyle M. (2023-04-06). "Understanding the Genetic Risk of IDH-Mutant Glioma". The New England Journal of Medicine. 388 (14): 1332–1334. doi:10.1056/NEJMcibr2213112. ISSN 1533-4406. PMID 37018498.
  33. ↑ Watanabe, Takuya; Vital, Anne; Nobusawa, Sumihito; Kleihues, Paul; Ohgaki, Hiroko (2009-06). "Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome". Acta Neuropathologica. 117 (6): 653–656. doi:10.1007/s00401-009-0528-x. ISSN 1432-0533. PMID 19340432. {{cite journal}}: Check date values in: |date= (help)
  34. ↑ Watanabe, Takuya; Vital, Anne; Nobusawa, Sumihito; Kleihues, Paul; Ohgaki, Hiroko (2009-06). "Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome". Acta Neuropathologica. 117 (6): 653–656. doi:10.1007/s00401-009-0528-x. ISSN 1432-0533. PMID 19340432. {{cite journal}}: Check date values in: |date= (help)
  35. ↑ Corvino, Sergio; Mariniello, Giuseppe; Corazzelli, Giuseppe; Franca, Raduan Ahmed; Del Basso De Caro, Marialaura; Della Monica, Rosa; Chiariotti, Lorenzo; Maiuri, Francesco (2022-07-16). "Brain Gliomas and Ollier Disease: Molecular Findings as Predictive Risk Factors?". Cancers. 14 (14): 3464. doi:10.3390/cancers14143464. ISSN 2072-6694. PMC 9324397. PMID 35884525.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  36. ↑ Richardson, Timothy E.; Yokoda, Raquel T.; Rashidipour, Omid; Vij, Meenakshi; Snuderl, Matija; Brem, Steven; Hatanpaa, Kimmo J.; McBrayer, Samuel K.; Abdullah, Kalil G. (2023). "Mismatch repair protein mutations in isocitrate dehydrogenase (IDH)-mutant astrocytoma and IDH-wild-type glioblastoma". Neuro-Oncology Advances. 5 (1): vdad085. doi:10.1093/noajnl/vdad085. ISSN 2632-2498. PMC 10406418. PMID 37554222.{{cite journal}}: CS1 maint: article number as page number (link)

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