CNS5:Astrocytoma, IDH-mutant: Difference between revisions

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{{DISPLAYTITLE:Astrocytoma, IDH-mutant}}
{{DISPLAYTITLE:Astrocytoma, IDH-mutant}}
[[CNS5:Table_of_Contents|Central Nervous System Tumours (WHO Classification, 5th ed.)]]
[[CNS5:Table_of_Contents|Central Nervous System Tumours (WHO Classification, 5th ed.)]]


{{Under Construction}}
{{Under Construction}}
<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
==Primary Author(s)*==
==Primary Author(s)*==
Put your text here<span style="color:#0070C0"> (''<span class="blue-text">EXAMPLE:</span>'' Jane Smith, PhD) </span>
Meenakshi Mehrotra, PhD, Mount Sinai Health System, New York
==WHO Classification of Disease==
==WHO Classification of Disease==


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==Gene Rearrangements==
==Gene Rearrangements==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
<br />
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|''MET''
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|''PTPRZ1::MET''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|N/A
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|N/A
|<span class="blue-text">EXAMPLE:</span>
|Rare (~1%)
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). BCR::ABL1 is generally favorable in CML (add reference).
|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>
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|
|<span class="blue-text">EXAMPLE:</span>
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|<span class="blue-text">EXAMPLE:</span>
|
 
|
Both balanced and unbalanced forms are observed by FISH (add references).
|
|-
|
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|
|
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|}
|}
==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
<br />
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|9
7
|loss
|<span class="blue-text">EXAMPLE:</span> Loss
|chr9:21,967,752-21,995,324
|<span class="blue-text">EXAMPLE:</span>
|''CDKN2A''
chr7
|P
|<span class="blue-text">EXAMPLE:</span>
|Yes  (WHO CNS5)
Unknown
|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>
|<span class="blue-text">EXAMPLE:</span> D, P
|<span class="blue-text">EXAMPLE:</span> No
|<span class="blue-text">EXAMPLE:</span>
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 references).
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|9
8
|loss
|<span class="blue-text">EXAMPLE:</span> Gain
|chr9:22,002,903-22,009,313
|<span class="blue-text">EXAMPLE:</span>
|''CDKN2B''
chr8
|P
|<span class="blue-text">EXAMPLE:</span>
|Yes  (WHO CNS5)
Unknown
|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>
|<span class="blue-text">EXAMPLE:</span> D, P
|-
|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''
|
|
|<span class="blue-text">EXAMPLE:</span>
|No
Common recurrent secondary finding for t(8;21) (add references).
|<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>
|-
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|<span class="blue-text">EXAMPLE:</span>
|
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
|
|
|
|
|
|-
|
|
|
|
|
|
|
|-
|-
|
|
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|}
|}
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
<br />
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|9p, 10q, 11p,  22q and 13q deletions
Co-deletion of 1p and 18q
|N/A
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|Rare
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|P
|<span class="blue-text">EXAMPLE:</span> D, 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>
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|CNLOH chr17p
Microsatellite instability - hypermutated
|N/A
|
|Rare
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|P
|<span class="blue-text">EXAMPLE:</span> P, T
|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)==
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
<br />
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|''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 />
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|Common
|<span class="blue-text">EXAMPLE:</span> Oncogene
|D
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|Yes (WHO CNS5)
|<span class="blue-text">EXAMPLE:</span> T
|Essential  diagnostic criterion (WHO CNS 5)
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
|''TP53''
|Variable LOF mutations
|TSG
<br />
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|Common
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|D
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|Yes (WHO CNS5)
|<span class="blue-text">EXAMPLE:</span> P
|Desirable  diagnostic criterion (WHO CNS 5)
|
|-
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|''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>
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|''PIK3CA''
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|Exon 10,  exon 21 activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|Rare
|<span class="blue-text">EXAMPLE:</span> T
|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.
|}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==
==Epigenomic Alterations==
Put your text here
''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==
==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 <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
Line 241: Line 333:
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|Homozygous deletion of ''CDKN2A'', ''CDKN2B'',  ''RB1'', and ''CDK4''
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|RB pathway
|<span class="blue-text">EXAMPLE:</span> 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>
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|Amp of ''PDGFRA'' and activating  mutations in PI3K genes
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|RTK-PI3K-mTOR
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|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>  
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|
|-
|-
|
|
Line 258: Line 350:
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
·      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==
==Familial Forms==
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
·      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>
==Additional Information==
 
Put your text here
·      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>
==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>
·      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==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>
<br />
[[Category:CNS5]]
[[Category:DISEASE]]
[[Category:Diseases A]]
<references />
==Notes==
==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.  
<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.  
Line 272: Line 378:
Prior Author(s):
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>.
<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>.
[[Category:CNS5]][[Category:DISEASE]][[Category:Diseases A]]

Latest revision as of 07:04, 4 September 2025


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]

References


  1. ↑ Liu, Lingyu; et al. (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 Check |pmc= value (help). PMID 37530224 Check |pmid= value (help). Check date values in: |date= (help)
  2. ↑ Wong, Queenie Hoi-Wing; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  3. ↑ Kirishima, Mari; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  4. ↑ Kirishima, Mari; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  5. ↑ Yang, Rui Ryan; et al. (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 Check |pmc= value (help). PMID 31733156. Check date values in: |date= (help)
  6. ↑ Lee, Kwanghoon; et al. (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 Check |pmc= value (help). PMID 37185778 Check |pmid= value (help).
  7. ↑ Yang, Rui Ryan; et al. (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 Check |pmc= value (help). PMID 31733156. Check date values in: |date= (help)
  8. ↑ Shirahata, Mitsuaki; et al. (2018-07). "Novel, improved grading system(s) for IDH-mutant astrocytic gliomas". Acta Neuropathologica. 136 (1): 153–166. doi:10.1007/s00401-018-1849-4. ISSN 1432-0533. PMID 29687258. Check date values in: |date= (help)
  9. ↑ Yang, Rui Ryan; et al. (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 Check |pmc= value (help). PMID 31733156. Check date values in: |date= (help)
  10. ↑ Shirahata, Mitsuaki; et al. (2018-07). "Novel, improved grading system(s) for IDH-mutant astrocytic gliomas". Acta Neuropathologica. 136 (1): 153–166. doi:10.1007/s00401-018-1849-4. ISSN 1432-0533. PMID 29687258. Check date values in: |date= (help)
  11. ↑ Lee, Kwanghoon; et al. (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 Check |pmc= value (help). PMID 37185778 Check |pmid= value (help).
  12. ↑ Li, Kay Ka-Wai; et al. (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.
  13. ↑ Lee, Kwanghoon; et al. (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 Check |pmc= value (help). PMID 37185778 Check |pmid= value (help).
  14. ↑ Tesileanu, C. Mircea S.; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  15. ↑ Mirchia, Kanish; et al. (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 Check |pmc= value (help). PMID 32640746 Check |pmid= value (help).
  16. ↑ Tesileanu, C. Mircea S.; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  17. ↑ Tesileanu, C. Mircea S.; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  18. ↑ Cancer Genome Atlas Research Network; et al. (2015-06-25). "Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas". The New England Journal of Medicine. 372 (26): 2481–2498. doi:10.1056/NEJMoa1402121. ISSN 1533-4406. PMC 4530011. PMID 26061751.
  19. ↑ Eckel-Passow, Jeanette E.; et al. (2015-06-25). "Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors". The New England Journal of Medicine. 372 (26): 2499–2508. doi:10.1056/NEJMoa1407279. ISSN 1533-4406. PMC 4489704. PMID 26061753.
  20. ↑ Killela, Patrick J.; et al. (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; et al. (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 Check |pmc= value (help). PMID 37530224 Check |pmid= value (help). Check date values in: |date= (help)
  22. ↑ Aoki, Kosuke; et al. (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; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  24. ↑ Wong, Queenie Hoi-Wing; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  25. ↑ Aoki, Kosuke; et al. (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; et al. (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 Check |pmc= value (help). PMID 35287567 Check |pmid= value (help).
  27. ↑ Nakamura, M.; et al. (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. Check date values in: |date= (help)
  28. ↑ Turcan, Sevin; et al. (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.; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  30. ↑ Tesileanu, C. Mircea S.; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  31. ↑ Batchelor, Tracy T.; et al. (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 Check |pmid= value (help).
  32. ↑ Batchelor, Tracy T.; et al. (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 Check |pmid= value (help).
  33. ↑ Watanabe, Takuya; et al. (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. Check date values in: |date= (help)
  34. ↑ Watanabe, Takuya; et al. (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. Check date values in: |date= (help)
  35. ↑ Corvino, Sergio; et al. (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 Check |pmc= value (help). PMID 35884525 Check |pmid= value (help).
  36. ↑ Richardson, Timothy E.; et al. (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 Check |pmc= value (help). PMID 37554222 Check |pmid= value (help).

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