Compendium of Cancer Genome Aberrations

Changes

CNS5:Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (view source)

Revision as of 13:52, 25 February 2024

11,687 bytes added ,  25 February
m
Jennelleh moved page Diffuse Paediatric-Type High-Grade Glioma, H3-Wildtype and IDH-Wildtype to CNS5:Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype without leaving a redirect: Move to CNS5
Line 1: Line 1: −
{{Under Construction}}
+
<br />
 
==Primary Author(s)*==
 
==Primary Author(s)*==
   −
Put your text here
+
Madina Sukhanova, PhD FACMG Northwestern University
    
__TOC__
 
__TOC__
Line 8: Line 8:  
==Cancer Category/Type==
 
==Cancer Category/Type==
   −
Put your text here
+
Glioma
    
==Cancer Sub-Classification / Subtype==
 
==Cancer Sub-Classification / Subtype==
   −
Put your text here
+
Paediatric-type diffuse high-grade gliomas with three molecular subtypes: RTK2, RTK1, and MYCN
    
==Definition / Description of Disease==
 
==Definition / Description of Disease==
   −
Put your text here
+
This is a distinct entity in the World Health Organization (WHO) classification system within the section of paediatric-type diffuse high-grade gliomas. Distinct methylation profiles and molecular alterations define three subtypes: dpHGG RTK1, dpHGG RTK2, and dpHGG MYCN. Gliomas arising after therapeutic radiation are predominantly of the pHGG RTK1 subtype. Known tumorigenic drivers include TP53, MYCN, ID2, and genes from RAS/MAPK and PI3K pathways.<ref>{{Cite journal|last=Buczkowicz|first=Pawel|last2=Hoeman|first2=Christine|last3=Rakopoulos|first3=Patricia|last4=Pajovic|first4=Sanja|last5=Letourneau|first5=Louis|last6=Dzamba|first6=Misko|last7=Morrison|first7=Andrew|last8=Lewis|first8=Peter|last9=Bouffet|first9=Eric|date=2014-05|title=Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations|url=https://pubmed.ncbi.nlm.nih.gov/24705254|journal=Nature Genetics|volume=46|issue=5|pages=451–456|doi=10.1038/ng.2936|issn=1546-1718|pmc=3997489|pmid=24705254}}</ref> <ref>{{Cite journal|last=Sturm|first=Dominik|last2=Orr|first2=Brent A.|last3=Toprak|first3=Umut H.|last4=Hovestadt|first4=Volker|last5=Jones|first5=David T. W.|last6=Capper|first6=David|last7=Sill|first7=Martin|last8=Buchhalter|first8=Ivo|last9=Northcott|first9=Paul A.|date=2016-02-25|title=New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs|url=https://pubmed.ncbi.nlm.nih.gov/26919435|journal=Cell|volume=164|issue=5|pages=1060–1072|doi=10.1016/j.cell.2016.01.015|issn=1097-4172|pmc=5139621|pmid=26919435}}</ref> <ref name=":0">{{Cite journal|last=Korshunov|first=Andrey|last2=Ryzhova|first2=Marina|last3=Hovestadt|first3=Volker|last4=Bender|first4=Sebastian|last5=Sturm|first5=Dominik|last6=Capper|first6=David|last7=Meyer|first7=Jochen|last8=Schrimpf|first8=Daniel|last9=Kool|first9=Marcel|date=2015-05|title=Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers|url=https://pubmed.ncbi.nlm.nih.gov/25752754|journal=Acta Neuropathologica|volume=129|issue=5|pages=669–678|doi=10.1007/s00401-015-1405-4|issn=1432-0533|pmid=25752754}}</ref> <ref name=":1">{{Cite journal|last=Mackay|first=Alan|last2=Burford|first2=Anna|last3=Carvalho|first3=Diana|last4=Izquierdo|first4=Elisa|last5=Fazal-Salom|first5=Janat|last6=Taylor|first6=Kathryn R.|last7=Bjerke|first7=Lynn|last8=Clarke|first8=Matthew|last9=Vinci|first9=Mara|date=2017-10-09|title=Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma|url=https://pubmed.ncbi.nlm.nih.gov/28966033|journal=Cancer Cell|volume=32|issue=4|pages=520–537.e5|doi=10.1016/j.ccell.2017.08.017|issn=1878-3686|pmc=5637314|pmid=28966033}}</ref>
    
==Synonyms / Terminology==
 
==Synonyms / Terminology==
   −
Put your text here
+
None
    
==Epidemiology / Prevalence==
 
==Epidemiology / Prevalence==
   −
Put your text here
+
The 2021 WHO classified this entity as pediatric-type, based on well defined studies focusing on a pediatric population with gliomas characterised by IDH-/H3-wildtype status<ref name=":1" /><ref>{{Cite journal|last=Mackay|first=Alan|last2=Burford|first2=Anna|last3=Molinari|first3=Valeria|last4=Jones|first4=David T. W.|last5=Izquierdo|first5=Elisa|last6=Brouwer-Visser|first6=Jurriaan|last7=Giangaspero|first7=Felice|last8=Haberler|first8=Christine|last9=Pietsch|first9=Torsten|date=2018-05-14|title=Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial|url=https://pubmed.ncbi.nlm.nih.gov/29763623|journal=Cancer Cell|volume=33|issue=5|pages=829–842.e5|doi=10.1016/j.ccell.2018.04.004|issn=1878-3686|pmc=5956280|pmid=29763623}}</ref><ref name=":2">{{Cite journal|last=Korshunov|first=Andrey|last2=Schrimpf|first2=Daniel|last3=Ryzhova|first3=Marina|last4=Sturm|first4=Dominik|last5=Chavez|first5=Lukas|last6=Hovestadt|first6=Volker|last7=Sharma|first7=Tanvi|last8=Habel|first8=Antje|last9=Burford|first9=Anna|date=2017-09|title=H3-/IDH-wild type pediatric glioblastoma is comprised of molecularly and prognostically distinct subtypes with associated oncogenic drivers|url=https://pubmed.ncbi.nlm.nih.gov/28401334|journal=Acta Neuropathologica|volume=134|issue=3|pages=507–516|doi=10.1007/s00401-017-1710-1|issn=1432-0533|pmid=28401334}}</ref>. Therefore, the frequency of this tumor type in adults in unknown. The median reported age of patients at the time of diagnosis was 9.8 years. One study reported male prevalence.<ref name=":2" />
    
==Clinical Features==
 
==Clinical Features==
   −
Put your text here and fill in the table
+
The clinical features are dependent on the tumour location. Symptoms can include seizures and motor or sensory deficits.
 
{| class="wikitable"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
−
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+
|Seizures and motor or sensory deficits.
−
 
  −
EXAMPLE B-symptoms (weight loss, fever, night sweats)
  −
 
  −
EXAMPLE Fatigue
  −
 
  −
EXAMPLE Lymphadenopathy (uncommon)
   
|-
 
|-
−
|'''Laboratory Findings'''
+
|'''Imaging Findings'''
−
|EXAMPLE Cytopenias
+
|MRI characteristics are comparable to other high-grade glioma tumour types. MRI typically reveals well-defined margins and homogeneous contrast-enhancement and mild perilesional edema.<ref name=":3">{{Cite journal|last=Tauziède-Espariat|first=A.|last2=Debily|first2=M.-A.|last3=Castel|first3=D.|last4=Grill|first4=J.|last5=Puget|first5=S.|last6=Roux|first6=A.|last7=Saffroy|first7=R.|last8=Pagès|first8=M.|last9=Gareton|first9=A.|date=2020-07-09|title=The pediatric supratentorial MYCN-amplified high-grade gliomas methylation class presents the same radiological, histopathological and molecular features as their pontine counterparts|url=https://pubmed.ncbi.nlm.nih.gov/32646492|journal=Acta Neuropathologica Communications|volume=8|issue=1|pages=104|doi=10.1186/s40478-020-00974-x|issn=2051-5960|pmc=7346460|pmid=32646492}}</ref><ref>{{Cite journal|last=Tauziède-Espariat|first=A.|last2=Debily|first2=M.-A.|last3=Castel|first3=D.|last4=Grill|first4=J.|last5=Puget|first5=S.|last6=Sabel|first6=M.|last7=Blomgren|first7=K.|last8=Gareton|first8=A.|last9=Dangouloff-Ros|first9=V.|date=2019-06-10|title=An integrative radiological, histopathological and molecular analysis of pediatric pontine histone-wildtype glioma with MYCN amplification (HGG-MYCN)|url=https://pubmed.ncbi.nlm.nih.gov/31177990|journal=Acta Neuropathologica Communications|volume=7|issue=1|pages=87|doi=10.1186/s40478-019-0738-y|issn=2051-5960|pmc=6556947|pmid=31177990}}</ref>
−
 
  −
EXAMPLE Lymphocytosis (low level)
   
|}
 
|}
    
==Sites of Involvement==
 
==Sites of Involvement==
   −
Put your text here
+
Main site: supratentorial brain.
 +
 
 +
Other sites: brainstem, and cerebellum.<ref name=":2" />
 +
 
 +
Although most of molecular subtypes of dpHGG involve the supratentorial compartment (96% of dpHGG RTK2; 86% of dpHGG MYCN; 82% of dpHGG RTK1 tumors),  a lesser proporton can involve infratentorial/brainstem sites (4% of dpHGG RTK2;14% of dpHGG MYCN; 18% of dpHGG RTK1 cases).<ref name=":2" />
    
==Morphologic Features==
 
==Morphologic Features==
   −
Put your text here
+
The morphology of dHGGs, H3-/IDH-wildtype, shows glioblastoma-like features with high cellularity, mitotic activity, microvascular proliferation, and necrosis; however, undifferentiated, primitive morphology and areas of glial differentiation can also be noted within the same case. The pHGG MYCN molecular subtype often consists of large cells with distinct nucleoli admixed with spindle-shaped and epithelioid cells; the architecture of these tumours can show areas of diffuse infiltration, in combinaiton with circumscribed nodules.<ref name=":3" />
    
==Immunophenotype==
 
==Immunophenotype==
−
  −
Put your text here and fill in the table
      
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 61: Line 55:  
!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
−
|Positive (universal)||EXAMPLE CD1
+
|Positive (universal)||Neoplastic glial component – GFAP, and/or OLIG2<ref name=":0" /><ref name=":1" />
 
|-
 
|-
−
|Positive (subset)||EXAMPLE CD2
+
|Positive (subset)||dpHGG MYCN molecular subtype can be positive for neuronal markers
 
|-
 
|-
−
|Negative (universal)||EXAMPLE CD3
+
|Negative (universal)|| IDH1 R132H
 +
H3 p.K28me3 (K27me3) (preserved expression)<ref name=":3" />
 
|-
 
|-
−
|Negative (subset)||EXAMPLE CD4
+
|Negative (subset)||dpHGG MYCN molecular subtype can be negative for glial marker GFAP, and/or OLIG2
 
|}
 
|}
    
==Chromosomal Rearrangements (Gene Fusions)==
 
==Chromosomal Rearrangements (Gene Fusions)==
−
 
+
Fusions listed in the table below were identified in a single study, thus, frequencies in dpHGG H3/IGH-wt should be interpreted with caution.<ref name=":4">{{Cite journal|last=Deng|first=Maximilian Y.|last2=Sturm|first2=Dominik|last3=Pfaff|first3=Elke|last4=Sill|first4=Martin|last5=Stichel|first5=Damian|last6=Balasubramanian|first6=Gnana Prakash|last7=Tippelt|first7=Stephan|last8=Kramm|first8=Christof|last9=Donson|first9=Andrew M.|date=2021-09-20|title=Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B|url=https://pubmed.ncbi.nlm.nih.gov/34545083|journal=Nature Communications|volume=12|issue=1|pages=5530|doi=10.1038/s41467-021-25708-y|issn=2041-1723|pmc=8452680|pmid=34545083}}</ref>
−
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
+
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Structural  variation!!Prevalence
 
!Diagnostic Significance (Yes, No or Unknown)
 
!Diagnostic Significance (Yes, No or Unknown)
 
!Prognostic Significance (Yes, No or Unknown)
 
!Prognostic Significance (Yes, No or Unknown)
Line 82: Line 75:  
!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+
|t(3;3)(p21.31;p25.2)
−
EXAMPLE 30% (add reference)
+
|FYCO1::RAF1
−
|Yes
+
|deletion
−
|No
+
|11%<ref name=":4" />
−
|Yes
+
|Unknown
−
|EXAMPLE
+
|Unknown
−
 
+
|Unknown
−
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).
+
|Results in constitutive activation of kinase domain<ref name=":4" />
 +
|-
 +
|t(7;7)(q31.2;q31.32)||PTPRZ1::MET||deletion||22%<ref name=":4" />
 +
|Unknown
 +
|Unknown
 +
|Unknown
 +
|Concurrent MET amp is frequently noted<ref name=":4" />
 +
|-
 +
|t(7;7)(q31.2;q31.32)
 +
|CAPZA2::MET
 +
|deletion
 +
|11%<ref name=":4" />
 +
|Unknown
 +
|Unknown
 +
|Unknown
 +
|Concurrent MET amp is frequently noted<ref name=":4" />
 +
|-
 +
|t(9;9)(p31.32;p21.33)
 +
|GKAP1::NTRK2
 +
|deletion
 +
|11%<ref name=":4" />
 +
|Unknown
 +
|Unknown
 +
|Unknown
 +
|Results in constitutive dimerization of receptor<ref name=":4" />
 
|}
 
|}
 
 
 
==Individual Region Genomic Gain/Loss/LOH==
 
==Individual Region Genomic Gain/Loss/LOH==
−
  −
Put your text here and fill in the table
      
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 104: Line 119:  
!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
+
|2
−
 
+
|Amplification
−
7
+
|chr2:15,940,550-15,947,004 [GRCh38]
−
|EXAMPLE Loss
+
|2p24.3
−
|EXAMPLE
+
|Yes [50% dpHGG MYCN subtype]
−
 
+
|Worse OS<ref name=":1" /><ref name=":2" />
−
chr7:1- 159,335,973 [hg38]
+
|Unknown
−
|EXAMPLE
+
|MYCN amplification<ref name=":2" /><ref name=":5">{{Cite journal|last=Capper|first=David|last2=Jones|first2=David T. W.|last3=Sill|first3=Martin|last4=Hovestadt|first4=Volker|last5=Schrimpf|first5=Daniel|last6=Sturm|first6=Dominik|last7=Koelsche|first7=Christian|last8=Sahm|first8=Felix|last9=Chavez|first9=Lukas|date=2018-03-22|title=DNA methylation-based classification of central nervous system tumours|url=https://pubmed.ncbi.nlm.nih.gov/29539639|journal=Nature|volume=555|issue=7697|pages=469–474|doi=10.1038/nature26000|issn=1476-4687|pmc=6093218|pmid=29539639}}</ref>
−
 
+
|-
−
chr7
+
|2
−
|Yes
+
|Amplification
−
|Yes
+
|chr2:8,682,056-8,684,461 [GRCh38]
 +
|2p25.1
 +
|No, but recurrent secondary finding [66% of dpHGG MYCN subtype]
 +
|Unknown
 +
|Unknown
 +
|ID2 amplification is often (66%) co-amplified with MYCN<ref name=":2" /><ref name=":5" />
 +
|-
 +
|4
 +
|Amplification/Mutation
 +
|chr4:51819533-54425718 [GRCh38]
 +
|4q12
 +
|Yes [33% of dpHGG RTK1 subtype]
 +
|No<ref name=":2" />
 +
|Unknown
 +
|PDGFRA alterations<ref name=":2" /><ref name=":6">WHO Classification of Tumours Editorial Board. Central nervous system tumours. Lyon (France): International Agency for Research on Cancer; 2021. (WHO classification of tumours series, 5th ed.; vol. 6). <nowiki>https://publications.iarc.fr/601</nowiki>.</ref>
 +
|-
 +
|7
 +
|Amplification
 +
|chr7:55,019,017-55,211,628 [GRCh38]
 +
|7p11.2
 +
|Yes [50% of dpHGG RTK2 subtype]
 +
|No<ref name=":2" />
 +
|Unknown
 +
|EGFR amplification<ref name=":2" />
 +
|-
 +
|8
 +
|Amplification
 +
|chr8:127,736,231-127,742,951 [GRCh38]
 +
|8q24.21
 +
|No, but recurrent in dpHGG MYCN subtype [8%]
 +
|Unknown
 +
|Unknown
 +
|MYC amplification<ref name=":2" />
 +
|-
 +
|9
 +
|Homozygous loss
 +
|CDKN2A - chr9:21,967,752-21,995,324 [GRCh38]
 +
CDKN2B - chr9: ''9:''22,002,903-22,009,313  [GRCh38]
 +
|9p21.3
 
|No
 
|No
−
|EXAMPLE
+
|Worse outcome<ref name=":2" />
−
 
+
|Unknown
−
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).
+
|Deletions result in bi-allelic loss of CDKN2A/B seen in 6% MYCN subtype, 27% RTK1 subtype; 72% RTK2 subtype.<ref name=":2" /><ref name=":4" />
 
|-
 
|-
−
|EXAMPLE
+
|12 / 7
−
 
+
|Amplification
−
8
+
|CDK4 - chr12:57,747,727-57,752,310 [GRCh38]
−
|EXAMPLE Gain
+
CDK6 - chr7:92,604,921-92,836,573 [GRCh38]
−
|EXAMPLE
+
|12q14.1 / 7q21.2
−
 
  −
chr8:1-145,138,636 [hg38]
  −
|EXAMPLE
  −
 
  −
chr8
   
|No
 
|No
−
|No
+
|Unknown
−
|No
+
|Unknown
−
|EXAMPLE
+
|Ampifications of CDK4/6 seen in 22% MYCN subtype, 9% RTK1 subtype; 17% RTK2 subtype.<ref name=":2" />
−
 
  −
Common recurrent secondary finding for t(8;21) (add reference).
   
|}
 
|}
 
==Characteristic Chromosomal Patterns==
 
==Characteristic Chromosomal Patterns==
−
  −
Put your text here
      
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 150: Line 194:  
!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
+
|Chromosome 7 gain
−
 
+
|No
−
Co-deletion of 1p and 18q
   
|Yes
 
|Yes
 +
|No
 +
|Recurrent finding in 47% MYCN subtype; 12% RTK1 subtype; 28% RTK2 subtype.<ref name=":2" />
 +
|-
 +
|Chromosome 10q loss
 
|No
 
|No
 
|No
 
|No
−
|EXAMPLE:
+
|No
−
 
+
|Recurrent finding in 42% MYCN subtype; 12% RTK1 subtype; 50% RTK2 subtype.<ref name=":2" />
−
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
   
|}
 
|}
 
==Gene Mutations (SNV/INDEL)==
 
==Gene Mutations (SNV/INDEL)==
−
  −
Put your text here and fill in the table
      
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 172: Line 216:  
!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE: TP53; Variable LOF mutations
+
|PDGFRA
−
 
+
|Receptor
−
EXAMPLE:
+
|Not stated in literature; referred to in the WHO Classification<ref name=":6" />
−
 
+
|unclear
−
EGFR; Exon 20 mutations
+
|IDH1/2, H3<br />
−
 
+
|Unknown
−
EXAMPLE: BRAF; Activating mutations
+
|Unknown
−
|EXAMPLE: TSG
+
|Unknown
−
|EXAMPLE: 20% (COSMIC)
  −
 
  −
EXAMPLE: 30% (add Reference)
  −
|EXAMPLE: IDH1 R123H
  −
|EXAMPLE: EGFR amplification
   
|
 
|
 +
|-
 +
|TERT promoter
 +
|Enzyme/ acts as TCG
 +
|26% MYCN subtype; 64% RTK2 subtype<ref name=":2" />
 +
|unclear
 +
|IDH1/2, H3
 +
|Unknown
 +
|Unknown
 +
|Unknown
 
|
 
|
 +
|-
 +
|TP53
 +
|TSG
 +
|67% MYCN subtype; 48% RTK1 subtype; 50% RTK2 subtype<ref name=":2" /><ref name=":4" />
 +
|unclear
 +
|IDH1/2, H3
 +
|Unknown
 +
|Unknown
 +
|Unknown
 
|
 
|
−
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
  −
<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.
 
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.
Line 195: Line 250:  
==Epigenomic Alterations==
 
==Epigenomic Alterations==
   −
Put your text here
+
Methylation profiling can be used in the diagnosis of this tumor entity and can help to differentiate between three molecular profiles, pHGG RTK1, pHGG RTK2, and pHGG MYCN. Methylation of MGMT has been noted in 11% of pHGG MYCN cases and 18% of RTK1 cases.<ref name=":2" /> ''MGMT'' promoter methylation can be seen in 18% of the RTK1 subtype, 11% in the MYCN subtype and is rare in the RTK2 subtype.
    
==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
   −
Put your text here and fill in the table
+
The pHGG, H3/IDH-wildtype frequently reveals variants in genes encoding members of the TAS/MAPK and PI3K pathways.<ref name=":4" />
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
−
|EXAMPLE: BRAF and MAP2K1; Activating mutations
+
|MET; activating alterations
−
|EXAMPLE: MAPK signaling
+
|MAPK/ERK pathway activation
−
|EXAMPLE: Increased cell growth and proliferation
+
|Increased cell growth and proliferation
 
|-
 
|-
−
|EXAMPLE: CDKN2A; Inactivating mutations
+
|RAF1; activating alterations
−
|EXAMPLE: Cell cycle regulation
+
|MAPK/ERK pathway activation
−
|EXAMPLE: Unregulated cell division
+
|Increased cell growth and proliferation
 
|-
 
|-
−
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+
|NTRK2; activating alterations
−
|EXAMPLE:  Histone modification, chromatin remodeling
+
|MAPK/ERK pathway activation
−
|EXAMPLE:  Abnormal gene expression program
+
|Increased cell growth and proliferation
 
|}
 
|}
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
   −
Put your text here
+
*Chromosome microarray  
 +
*Next generation sequencing  
 +
*DNA methylation profiling
    
==Familial Forms==
 
==Familial Forms==
   −
Put your text here
+
Germline mutations of genes involved in the mismatch repair (MMR) system can be associated with a proportion of pHGG cases,<ref>{{Cite journal|last=Dodgshun|first=Andrew J.|last2=Fukuoka|first2=Kohei|last3=Edwards|first3=Melissa|last4=Bianchi|first4=Vanessa J.|last5=Das|first5=Anirban|last6=Sexton-Oates|first6=Alexandra|last7=Larouche|first7=Valérie|last8=Vanan|first8=Magimairajan I.|last9=Lindhorst|first9=Scott|date=2020-11|title=Germline-driven replication repair-deficient high-grade gliomas exhibit unique hypomethylation patterns|url=https://pubmed.ncbi.nlm.nih.gov/32895736|journal=Acta Neuropathologica|volume=140|issue=5|pages=765–776|doi=10.1007/s00401-020-02209-8|issn=1432-0533|pmid=32895736}}</ref><ref>{{Cite journal|last=Alphones|first=Sheena|last2=Chatterjee|first2=Uttara|last3=Singh|first3=Angad|last4=Das|first4=Anirban|last5=Zameer|first5=Lateef|last6=Achari|first6=Rimpa|last7=Bhattacharya|first7=Arpita|last8=Roy|first8=Paromita|date=2021-08|title=Immunohistochemical screening for mismatch repair protein deficiency in paediatric high-grade gliomas - institutional experience and review of literature|url=https://pubmed.ncbi.nlm.nih.gov/34097097|journal=Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery|volume=37|issue=8|pages=2521–2530|doi=10.1007/s00381-021-05229-1|issn=1433-0350|pmid=34097097}}</ref><ref>{{Cite journal|last=Amayiri|first=Nisreen|last2=Tabori|first2=Uri|last3=Campbell|first3=Brittany|last4=Bakry|first4=Doua|last5=Aronson|first5=Melyssa|last6=Durno|first6=Carol|last7=Rakopoulos|first7=Patricia|last8=Malkin|first8=David|last9=Qaddoumi|first9=Ibrahim|date=2016-01-15|title=High frequency of mismatch repair deficiency among pediatric high grade gliomas in Jordan|url=https://pubmed.ncbi.nlm.nih.gov/26293621|journal=International Journal of Cancer|volume=138|issue=2|pages=380–385|doi=10.1002/ijc.29724|issn=1097-0215|pmid=26293621}}</ref> typically of the pHGG RTK1 subtype.
−
 
  −
==Additional Information==
  −
 
  −
Put your text here
  −
 
  −
==Links==
  −
 
  −
Put your text placeholder here (use "Link" icon at top of page)
      
==References==
 
==References==
 
<references />
 
<references />
−
(use "Cite" icon at top of page)
+
<br />
−
===EXAMPLE Book===
  −
 
  −
#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.
  −
 
   
==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 CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 
<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.
Retrieved from "https://ccga.io/index.php/Special:MobileDiff/11715...14244"