Compendium of Cancer Genome Aberrations

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[[CNS5:Table_of_Contents|Central Nervous System Tumours (WHO Classification, 5th ed.)]]
==Primary Author(s)*==
 
__TOC__
 
==Cancer Category/Type==
 
Put your text here
 
==Cancer Sub-Classification / Subtype==
 
Put your text here
 
==Definition / Description of Disease==
 
Put your text here
 
==Synonyms / Terminology==
 
Put your text here
 
==Epidemiology / Prevalence==
 
Put your text here
 
==Clinical Features==
 
Put your text here
 
==Sites of Involvement==
 
Put your text here
 
==Morphologic Features==
 
Put your text here


{{Under Construction}}
==Immunophenotype==


<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>
Put your text here and/or fill in the table
==Primary Author(s)*==
Wahab A. Khan, PhD, FACMG, Dartmouth Health <span style="color:#0070C0"> </span>
==WHO Classification of Disease==


{| class="wikitable"
{| class="wikitable sortable"
!Structure
!Disease
|-
|-
|Book
! Finding  !! Marker
|Central Nervous System Tumours (5th ed.)
|-
|-
|Category
|Positive (universal) || EXAMPLE CD1
|Gliomas, glioneuronal tumours, and neuronal tumours
|-
|-
|Family
|Positive (subset) || EXAMPLE CD2
|Gliomas, glioneuronal tumours, and neuronal tumours
|-
|-
|Type
|Negative (universal) || EXAMPLE CD3
|Circumscribed astrocytic gliomas
|-
|-
|Subtype(s)
|Negative (subset) || EXAMPLE CD4
|Pleomorphic xanthoastrocytoma
|}
|}


==Related Terminology==
==Chromosomal Rearrangements (Gene Fusions)==


{| class="wikitable"
Put your text here and/or fill in the table
|+
|Acceptable
|N/A
|-
|Not Recommended
|Pleomorphic xanthoastrocytoma with anaplastic features; anaplastic pleomorphic xanthoastrocytoma (for CNS WHO grade 3)
|}


==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>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
! Chromosomal Rearrangement !! Genes in Fusion (5’ or 3’ Segments) !! Pathogenic Derivative !! Prevalence
!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
|-
|-
|''BRAF''||''BRAF''-''KIAA1549'' (rare), ''RAF1'' fusions, ''NTRK2''/''ALK''/''NTRK1'' (very rare in PXA)||Aberrant MAPK pathway activation (i.e BRAF p.V600E variant)||N/A
|EXAMPLE t(9;22)(q34;q11.2) || EXAMPLE 3'ABL1 / 5'BCR || EXAMPLE der(22) || EXAMPLE 5%
|BRAF p.V600E: Common in PXA, Fusions: Rare
|D, P, T
|Yes (WHO 2021/2025, NCCN 2023)<ref>{{Cite journal|last=d’Amati|first=Antonio|last2=Bargiacchi|first2=Lavinia|last3=Rossi|first3=Sabrina|last4=Carai|first4=Andrea|last5=Bertero|first5=Luca|last6=Barresi|first6=Valeria|last7=Errico|first7=Maria Elena|last8=Buccoliero|first8=Anna Maria|last9=Asioli|first9=Sofia|date=2024-03-13|title=Pediatric CNS tumors and 2021 WHO classification: what do oncologists need from pathologists?|url=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2024.1268038/full|journal=Frontiers in Molecular Neuroscience|language=English|volume=17|doi=10.3389/fnmol.2024.1268038|issn=1662-5099}}</ref>
|BRAF p.V600E is diagnostic and predictive; kinase fusions targetable in rare cases<ref name=":0">{{Cite journal|last=Phillips|first=Joanna J.|last2=Gong|first2=Henry|last3=Chen|first3=Katharine|last4=Joseph|first4=Nancy M.|last5=van Ziffle|first5=Jessica|last6=Bastian|first6=Boris C.|last7=Grenert|first7=James P.|last8=Kline|first8=Cassie N.|last9=Mueller|first9=Sabine|date=2019-01|title=The genetic landscape of anaplastic pleomorphic xanthoastrocytoma|url=https://pubmed.ncbi.nlm.nih.gov/30051528|journal=Brain Pathology (Zurich, Switzerland)|volume=29|issue=1|pages=85–96|doi=10.1111/bpa.12639|issn=1750-3639|pmc=7837273|pmid=30051528}}</ref><ref>{{Cite journal|last=Vaubel|first=Rachael A.|last2=Caron|first2=Alissa A.|last3=Yamada|first3=Seiji|last4=Decker|first4=Paul A.|last5=Eckel Passow|first5=Jeanette E.|last6=Rodriguez|first6=Fausto J.|last7=Nageswara Rao|first7=Amulya A.|last8=Lachance|first8=Daniel|last9=Parney|first9=Ian|date=2018-03|title=Recurrent copy number alterations in low-grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC5807227/|journal=Brain Pathology (Zurich, Switzerland)|volume=28|issue=2|pages=172–182|doi=10.1111/bpa.12495|issn=1750-3639|pmc=5807227|pmid=28181325}}</ref> <ref>{{Cite journal|last=Tian|first=Lei|last2=Sun|first2=Wei|last3=Lou|first3=Lei|last4=Wang|first4=Wenyan|last5=Li|first5=Yanan|last6=Zhou|first6=Huandi|last7=Xiao|first7=Zhiqing|last8=Xue|first8=Xiaoying|date=2025|title=Pleomorphic xanthoastrocytoma with multiple recurrences and continuous malignant progression to bone metastasis: a case report|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC12174448/|journal=Frontiers in Surgery|volume=12|pages=1595199|doi=10.3389/fsurg.2025.1595199|issn=2296-875X|pmc=12174448|pmid=40535548}}</ref><ref>{{Cite journal|last=Di Nunno|first=Vincenzo|last2=Gatto|first2=Lidia|last3=Tosoni|first3=Alicia|last4=Bartolini|first4=Stefania|last5=Franceschi|first5=Enrico|date=2022|title=Implications of BRAF V600E mutation in gliomas: Molecular considerations, prognostic value and treatment evolution|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC9846085/|journal=Frontiers in Oncology|volume=12|pages=1067252|doi=10.3389/fonc.2022.1067252|issn=2234-943X|pmc=9846085|pmid=36686797}}</ref>
|-
|-
|''CDKN2A''/''B''
|EXAMPLE t(8;21)(q22;q22) || EXAMPLE 5'RUNX1 / 3'RUNXT1 || EXAMPLE der(8) || EXAMPLE 5%
|N/A
|}
|Loss leads to cell cycle dysregulation
|''CDKN2A''/''B'' homozygous deletion (9p21); chr7 gain; chr10/22 loss
==Characteristic Chromosomal Aberrations / Patterns==
|Common
 
|D, P
Put your text here
|Yes (WHO, NCCN—context specific)
 
|Co-occurrence with BRAF p.V600E supports PXA diagnosis
==Genomic Gain/Loss/LOH==
|-
|TERT
|N/A


|Telomerase activation (mainly in anaplastic PXA)
Put your text here and/or fill in the table
|TERT promoter mutations/amplifications
|'''Recurrent (15–47% in anaplastic) PMID: 30051528'''
|P (poor; recurrence risk)
|Yes (WHO, NCCN-context specefic)
|Seen mainly in grade 3/anaplastic; adverse outcome<ref name=":0" />


<br />
|-
|NTRK2, ALK, RAF1
|Fusions: NACC2-NTRK2, BEND5-NTRK2, PPP1CB-ALK, etc.
|MAPK pathway activation via kinase fusions
|Variable; not associated with classic chr alterations
|'''Rare (<5%) PMID: 37870438'''
|D
|Context-dependent ( e.g. For patients with CNS tumors who harbor NTRK fusions, TRK inhibitors such as larotrectinib or repotrectinib are considered a preferred therapy, regardless of histology, if other options are limited) NCCN CNS Cancer guidelines
|Reported in individual cases; more common in glioneuronal/low-grade gliomas
|}
==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>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
! Chromosome Number !! Gain/Loss/Amp/LOH !! Region
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|9p21
|EXAMPLE 8 || EXAMPLE Gain || EXAMPLE chr8:0-1000000
|Homozygous loss, LOH
|9p21.3; chr9:21,900,000-22,300,000 (GRCh38; ~400Kb)
|CDKN2A, CDKN2B
|D, P
|Yes (WHO CNS5, NCCN)
|'''Defining PXA feature; occurs in >85% of cases (PMID: 28181325)'''
|-
|-
|7
|EXAMPLE 7 || EXAMPLE Loss || EXAMPLE chr7:0-1000000
|Gain
|}
|Chr7 whole arm or segmental (varies)
|EGFR not typically amplified)
==Gene Mutations (SNV/INDEL)==
|D
 
|No (however, frequently mentioned in literature as a recurrent copy number change in PXA (PMID:
Put your text here and/or fill in the tables
|Trisomy, supports diagnosis; also seen in other gliomas
 
{| class="wikitable sortable"
|-
|-
|22
! Gene !! Mutation !! Oncogene/Tumor Suppressor/Other !! Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) !! Prevalence (COSMIC/TCGA/Other)
|Loss
|Whole chr22 (varied cytoband, arm)
|NF2, others
|D
|No (not guideline-specific, recurrent in PXA)
|Frequently reported, may occur with other losses
|-
|-
|8p
| EXAMPLE TP53 || EXAMPLE R273H || EXAMPLE Tumor Suppressor || EXAMPLE LOF || EXAMPLE 20%
|Loss
|}
|chr 8p (varied region)
|Varies
===Other Mutations===
|P
|No
|Seen in a subset, less common ((PMID: 28181325)
|-
|LOH
|Copy-neutral
|Varies (mainly 9p21)
|CDKN2A, CDKN2B
|D, P
|Yes (NCCN)
|copy-neutral LOH; supports diagnosis
|}
==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>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
! Type !! Gene/Region/Other
!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
|-
|-
|<span class="blue-text">EXAMPLE:</span>
| Concomitant Mutations || EXAMPLE IDH1 R123H
Co-deletion of 1p and 18q
|<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).
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|<span class="blue-text">EXAMPLE:</span> D, P
|
|
|-
|-
|<span class="blue-text">EXAMPLE:</span>
| Secondary Mutations || EXAMPLE Trisomy 7
Microsatellite instability - hypermutated
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|-
|
|Mutually Exclusive || EXAMPLE EGFR Amplification
|
|
|
|
|
|}
|}
==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>
{| class="wikitable sortable"
|-
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|BRAF


<br />
==Epigenomics (Methylation)==
|p.V600E missense activating mutation
 
|Oncogene
|Common (~60–80%)
|D, P, T
|Yes (WHO CNS5, NCCN)
|Specific for PXA, actionable with BRAF/MEK inhibitors; rarely found in diffuse astrocytomas. Favorable prognostic marker (PMID: 35545827).
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
|
|<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.
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|-
|
|
|
|
|
|
|
|}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==
Put your text here
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>
 
{| class="wikitable sortable"
Put your text here
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
==Diagnostic Testing Methods==
|-
 
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
Put your text here
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
 
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==
|-
 
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
Put your text here
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
 
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|<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
|-
|
|
|
|}
==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>
==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>
 
==Additional Information==
Put your text here
Put your text here
==Other Information==
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 links here
 
==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>
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.


Prior Author(s):
=== EXAMPLE Book ===
<nowiki>*</nowiki>''Citation of this Page'': “Pleomorphic xanthoastrocytoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/CNS5:Pleomorphic xanthoastrocytoma</nowiki>.
#Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4thedition.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.
[[Category:CNS5]]
 
[[Category:DISEASE]]
=== EXAMPLE Journal Article ===
[[Category:Diseases P]]
#Li Y, et al., (2001). Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 28:220-221, PMID 11431691.
<references />
 
== Notes ==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
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