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Line 1: − + − − Put your text here+ − Put your text here+ − Put your text here+ − Put your text here+ − Put your text here+ − Put your text here+ + + + + + + + + + + + + + − Put your text here+ + + − Put your text here+ − − Put your text here and/or fill in the table − + − + + + + + + + + + + + − + + − + + − + + + + + + + + + + + + + + + + + + + + + + − Put your text here and/or fill in the table+ + + + + + + + + + − {| class="wikitable sortable"+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + − ! Chromosomal Rearrangement !! Genes in Fusion (5’ or 3’ Segments) !! Pathogenic Derivative !! Prevalence+ + + + + + + + + − + + + + + + + + + + − + − + − + + + + + + + + + + − Put your text here+ + + + + + + + + + − ==Genomic Gain/Loss/LOH==+ + − Put your text here and/or fill in the table+ + + + + + + + + + + + − {| class="wikitable sortable"+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + − ! Chromosome Number !! Gain/Loss/Amp/LOH !! Region+ + + + + + + − + + + + + + + − + − + − + + + + + + + + + + + + + + + − Put your text here and/or fill in the tables+ + − {| class="wikitable sortable"+ + − ! Gene !! Mutation !! Oncogene/Tumor Suppressor/Other !! Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) !! Prevalence (COSMIC/TCGA/Other)+ − + − + − + − + − + − {| class="wikitable sortable"+ + + + + + + − ! Type !! Gene/Region/Other+ + + + + + + + + − + + + + + + + + + − + + + + + + + + + + + − + + + + + + + + + + + + + − Put your text here+ − Put your text here+ + + + + + + + + + + + + + + + + + + + + + + + + + − Put your text here+ − + − ==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==+ − − Put your text here − Put your text here+ − − − − Put your text here Line 135:
Line 488: − + − === EXAMPLE Book === − #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. − − === EXAMPLE Journal Article === − #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. − − == 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.
Jennelleh moved page Ganglioglioma to CNS5:Ganglioglioma without leaving a redirect: Move to GTS5
==Primary Author(s)*==
==Primary Author(s)*==
Dr Leila Moayed Alaei, Royal Prince Alfred Hospital
__TOC__
__TOC__
==Cancer Category/Type==
==Cancer Category/Type==
Glioneuronal tumour
==Cancer Sub-Classification / Subtype==
==Cancer Sub-Classification / Subtype==
Ganglioglioma
==Definition / Description of Disease==
==Definition / Description of Disease==
This is a distinct entity in the World Health Organization (WHO) classification system within the section of Gliomas, Glioneuronal and neuronal tumours. This is a well-differentiated glioneuronal tumour with low proliferative activity, comprised of mixed neoplastic neuronal and glial cell components. It is molecularly characterized by genomic aberrations causing MAPK pathway activation (CNS WHO grade 1)<ref name=":0">Solomon D.A. et al. (2021). Ganglioglioma, in "World Health Organization Classification of Central Nervous System Tumours" (5th edition). pp.111-115. </ref>.
==Synonyms / Terminology==
==Synonyms / Terminology==
None
==Epidemiology / Prevalence==
==Epidemiology / Prevalence==
Gangliogliomas are generally tumours of adolescent/young adults with a median age of 12 years at the time of diagnosis. However, the tumour has been reported in wider range of age from 0 to 70 years of age<ref>{{Cite journal|last=Lang|first=Shih-Shan|last2=Beslow|first2=Lauren A.|last3=Gabel|first3=Brandon|last4=Judkins|first4=Alex R.|last5=Fisher|first5=Michael J.|last6=Sutton|first6=Leslie N.|last7=Storm|first7=Phillip B.|last8=Heuer|first8=Gregory G.|date=2012-07|title=Surgical treatment of brain tumors in infants younger than six months of age and review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/22120270|journal=World Neurosurgery|volume=78|issue=1-2|pages=137–144|doi=10.1016/j.wneu.2011.09.012|issn=1878-8769|pmc=3292637|pmid=22120270}}</ref><ref name=":3">{{Cite journal|last=Blumcke|first=Ingmar|last2=Spreafico|first2=Roberto|last3=Haaker|first3=Gerrit|last4=Coras|first4=Roland|last5=Kobow|first5=Katja|last6=Bien|first6=Christian G.|last7=Pfäfflin|first7=Margarete|last8=Elger|first8=Christian|last9=Widman|first9=Guido|date=2017-10-26|title=Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery|url=https://pubmed.ncbi.nlm.nih.gov/29069555|journal=The New England Journal of Medicine|volume=377|issue=17|pages=1648–1656|doi=10.1056/NEJMoa1703784|issn=1533-4406|pmid=29069555}}</ref>. The tumour is more prevalent in male patients (59.8%) than in female patients (40.2%)<ref>{{Cite journal|last=Dudley|first=Roy W. R.|last2=Torok|first2=Michelle R.|last3=Gallegos|first3=Danielle R.|last4=Mulcahy-Levy|first4=Jean M.|last5=Hoffman|first5=Lindsey M.|last6=Liu|first6=Arthur K.|last7=Handler|first7=Michael H.|last8=Hankinson|first8=Todd C.|date=2015-03|title=Pediatric low-grade ganglioglioma: epidemiology, treatments, and outcome analysis on 348 children from the surveillance, epidemiology, and end results database|url=https://pubmed.ncbi.nlm.nih.gov/25603107|journal=Neurosurgery|volume=76|issue=3|pages=313–319; discussion 319; quiz 319–320|doi=10.1227/NEU.0000000000000619|issn=1524-4040|pmc=4333003|pmid=25603107}}</ref>.
==Clinical Features==
==Clinical Features==
The clinical features are dependent on the tumour location and size. If located in the cerebrum, the most common presentation is with focal seizures<ref name=":0" /><ref name=":1">{{Cite journal|last=Prayson|first=R. A.|last2=Khajavi|first2=K.|last3=Comair|first3=Y. G.|date=1995-07|title=Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors|url=https://pubmed.ncbi.nlm.nih.gov/7541447|journal=Journal of Neuropathology and Experimental Neurology|volume=54|issue=4|pages=513–520|doi=10.1097/00005072-199507000-00005|issn=0022-3069|pmid=7541447}}</ref>, with up to 23.6% of surgical epilepsy specimens harbouring gangliogliomas<ref>{{Cite journal|last=Blumcke|first=Ingmar|last2=Spreafico|first2=Roberto|last3=Haaker|first3=Gerrit|last4=Coras|first4=Roland|last5=Kobow|first5=Katja|last6=Bien|first6=Christian G.|last7=Pfäfflin|first7=Margarete|last8=Elger|first8=Christian|last9=Widman|first9=Guido|date=2017-10-26|title=Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery|url=https://pubmed.ncbi.nlm.nih.gov/29069555|journal=The New England Journal of Medicine|volume=377|issue=17|pages=1648–1656|doi=10.1056/NEJMoa1703784|issn=1533-4406|pmid=29069555}}</ref>. The mean duration of symptoms prior to diagnosis is also dependent on location. For tumours located in the cerebrum, the duration of symptoms prior to diagnosis ranges between 5 and 10 years, whereas in the brainstem and spinal cord, the mean duration of symptoms pre-diagnosis ranges between 1.25 years and 1.4 years, respectively<ref name=":1" /><ref name=":4">{{Cite journal|last=Lang|first=F. F.|last2=Epstein|first2=F. J.|last3=Ransohoff|first3=J.|last4=Allen|first4=J. C.|last5=Wisoff|first5=J.|last6=Abbott|first6=I. R.|last7=Miller|first7=D. C.|date=1993-12|title=Central nervous system gangliogliomas. Part 2: Clinical outcome|url=https://pubmed.ncbi.nlm.nih.gov/8246055|journal=Journal of Neurosurgery|volume=79|issue=6|pages=867–873|doi=10.3171/jns.1993.79.6.0867|issn=0022-3085|pmid=8246055}}</ref>.
The archetypal radiological features are of a circumscribed, solid/cystic mass, although varied appearances are the norm, ranging from presentation as a small cyst to a solid mass<ref name=":2">{{Cite journal|last=Zhang|first=D.|last2=Henning|first2=T. D.|last3=Zou|first3=L.-G.|last4=Hu|first4=L.-B.|last5=Wen|first5=L.|last6=Feng|first6=X.-Y.|last7=Dai|first7=S.-H.|last8=Wang|first8=W.-X.|last9=Sun|first9=Q.-R.|date=2008-01|title=Intracranial ganglioglioma: clinicopathological and MRI findings in 16 patients|url=https://pubmed.ncbi.nlm.nih.gov/18068794|journal=Clinical Radiology|volume=63|issue=1|pages=80–91|doi=10.1016/j.crad.2007.06.010|issn=0009-9260|pmid=18068794}}</ref>. Patterns of contrast enhancement can also vary, including enhancement of the cystic wall to a markedly enhanced nodule<ref name=":2" />.
{| class="wikitable"
|'''Signs and Symptoms'''
|Intracerebral ganglioglioma: Seizure; chronic temporal lobe epilepsy<ref name=":1" />
Brain stem ganglioglioma: blurry vision, loss of memory, syncope spells, cranial nerve deficits, headache, and gait instability<ref>{{Cite journal|last=Mpairamidis|first=Evriviadis|last2=Alexiou|first2=George A.|last3=Stefanaki|first3=Kalliopi|last4=Sfakianos|first4=George|last5=Prodromou|first5=Neofytos|date=2008-12|title=Brainstem ganglioglioma|url=https://pubmed.ncbi.nlm.nih.gov/19073857|journal=Journal of Child Neurology|volume=23|issue=12|pages=1481–1483|doi=10.1177/0883073808319316|issn=1708-8283|pmid=19073857}}</ref>
Spinal cord ganglioglioma: acute onset paraparesis<ref>{{Cite journal|last=Cruz|first=Thainá Zanon|last2=Ferreira-Pinto|first2=Pedro Henrique Costa|last3=Brito|first3=Ana Carolina Gonçalves|last4=Ururahy|first4=Leandro|last5=Sanchez|first5=Jefferson Trivino|last6=Nigri|first6=Flavio|date=2021|title=Ganglioglioma of the cervicothoracic spinal cord in a patient with neurofibromatosis type 1: A case report|url=https://pubmed.ncbi.nlm.nih.gov/34345454|journal=Surgical Neurology International|volume=12|pages=313|doi=10.25259/SNI_192_2021|issn=2229-5097|pmc=8326088|pmid=34345454}}</ref>
|-
|'''Imaging Findings'''
|Classic imaging features: T1 iso- to hypointense solid component, T2-hyperintense solid component with varied signal within the cystic component; nodule and cyst wall show variable contrast enhancement<ref name=":2" />
|}
==Sites of Involvement==
==Sites of Involvement==
Most common location: temporal lobes (>70%)<ref name=":1" /><ref name=":4" /><ref name=":5">{{Cite journal|last=Wolf|first=H. K.|last2=Müller|first2=M. B.|last3=Spänle|first3=M.|last4=Zentner|first4=J.|last5=Schramm|first5=J.|last6=Wiestler|first6=O. D.|date=1994|title=Ganglioglioma: a detailed histopathological and immunohistochemical analysis of 61 cases|url=https://pubmed.ncbi.nlm.nih.gov/7985497|journal=Acta Neuropathologica|volume=88|issue=2|pages=166–173|doi=10.1007/BF00294510|issn=0001-6322|pmid=7985497}}</ref>
Other locations: cerebrum, brainstem, cerebellum, spinal cord, and optic nerves, lateral ventricle<ref name=":3" /><ref name=":1" /><ref name=":4" /><ref name=":5" />[3,5,6,18]
==Morphologic Features==
==Morphologic Features==
Ganglioglioma is a biphasic tumour composed of a neoplastic neuronal and a neoplastic glial component<ref name=":3" /><ref name=":5" />. The neoplastic neuronal component is comprised of dysmorphic ganglion cells showing cytomegaly, binucleation and perimembranous aggregation of Nissl substance. Disorganised cytoarchitecture is also observed, with clustering of neurons. The neoplastic glial component can resemble a diffuse glioma or pilocytic astrocytoma; the glial component harbours the proliferative component of the tumour, which can show infiltration on microscopy. Proliferative activity is usually low to absent. The two components can be intermingled or geographically distinct. Other pertinent histological features include Rosenthal fibres, eosinophilic granular bodies and perivascular lymphoid infiltration<ref name=":3" /><ref name=":5" />[3,18]. An association with focal cortical dysplasia is a commonly reported finding<ref>{{Cite journal|last=Blümcke|first=Ingmar|last2=Thom|first2=Maria|last3=Aronica|first3=Eleonora|last4=Armstrong|first4=Dawna D.|last5=Vinters|first5=Harry V.|last6=Palmini|first6=Andre|last7=Jacques|first7=Thomas S.|last8=Avanzini|first8=Giuliano|last9=Barkovich|first9=A. James|date=2011-01|title=The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission|url=https://pubmed.ncbi.nlm.nih.gov/21219302|journal=Epilepsia|volume=52|issue=1|pages=158–174|doi=10.1111/j.1528-1167.2010.02777.x|issn=1528-1167|pmc=3058866|pmid=21219302}}</ref>.
==Immunophenotype==
==Immunophenotype==
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
! Finding !! Marker
!Finding!!Marker
|-
|-
|Positive (universal) || EXAMPLE CD1
|Positive (universal)
|CD34 expressed in expressed in ramified tumor cells<ref>{{Cite journal|last=Blümcke|first=Ingmar|last2=Wiestler|first2=Otmar D.|date=2002-07|title=Gangliogliomas: an intriguing tumor entity associated with focal epilepsies|url=https://pubmed.ncbi.nlm.nih.gov/12125736|journal=Journal of Neuropathology and Experimental Neurology|volume=61|issue=7|pages=575–584|doi=10.1093/jnen/61.7.575|issn=0022-3069|pmid=12125736}}</ref>
Neoplastic neuronal component – MAP2, neurofilament, synaptophysin, chromogranin A
*No definitive markers for neoplastic neuronal component
*Typical profile: chromogranin A+, NeuN-, synaptophysin+, neurofilament+, MAP2+ (but MAP2 - in glial component)<ref name=":0" /><ref>{{Cite journal|last=Blümcke|first=Ingmar|last2=Wiestler|first2=Otmar D.|date=2002-07|title=Gangliogliomas: an intriguing tumor entity associated with focal epilepsies|url=https://pubmed.ncbi.nlm.nih.gov/12125736|journal=Journal of Neuropathology and Experimental Neurology|volume=61|issue=7|pages=575–584|doi=10.1093/jnen/61.7.575|issn=0022-3069|pmid=12125736}}</ref>
Neoplastic glial component – GFAP, OLIG2 (MAP2 -)
*Ki-67 <5%<ref>{{Cite journal|last=Prayson|first=R. A.|last2=Khajavi|first2=K.|last3=Comair|first3=Y. G.|date=1995-07|title=Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors|url=https://pubmed.ncbi.nlm.nih.gov/7541447|journal=Journal of Neuropathology and Experimental Neurology|volume=54|issue=4|pages=513–520|doi=10.1097/00005072-199507000-00005|issn=0022-3069|pmid=7541447}}</ref>
|-
|-
|Positive (subset) || EXAMPLE CD2
|Positive (subset)
|BRAF VE1 (+ in BRAF-mutant gangliogliomas)<ref name=":0" />
|-
|-
|Negative (universal) || EXAMPLE CD3
|Negative (universal)
| IDH1 R132H, ATRX (normal retained pattern of staining)<ref name=":0" />
|-
|-
|Negative (subset) || EXAMPLE CD4
|Negative (subset)
|BRAF VE1 (- in BRAF-wildtype gangliogliomas)<ref name=":0" />
|}
|}
==Chromosomal Rearrangements (Gene Fusions)==
==Chromosomal Rearrangements (Gene Fusions)==
{| class="wikitable"
|'''Chromosomal Rearrangement'''
|'''Genes in Fusion'''
'''(5’ or 3’ Segments)'''
|'''Structural variation'''
|'''Prevalence'''
|'''Diagnostic Significance (Yes, No or Unknown)'''
|'''Prognostic Significance (Yes, No or Unknown)'''
|'''Therapeutic Significance (Yes, No or Unknown)'''
|'''Notes'''
|-
|t(7;7)(q34;q34)<ref name=":6">{{Cite journal|last=Pekmezci|first=Melike|last2=Villanueva-Meyer|first2=Javier E.|last3=Goode|first3=Benjamin|last4=Van Ziffle|first4=Jessica|last5=Onodera|first5=Courtney|last6=Grenert|first6=James P.|last7=Bastian|first7=Boris C.|last8=Chamyan|first8=Gabriel|last9=Maher|first9=Ossama M.|date=2018-06-07|title=The genetic landscape of ganglioglioma|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992851/|journal=Acta Neuropathologica Communications|volume=6|pages=47|doi=10.1186/s40478-018-0551-z|issn=2051-5960|pmc=5992851|pmid=29880043}}</ref><ref name=":7">{{Cite journal|last=Kim|first=Pora|last2=Zhou|first2=Xiaobo|date=2018-11-08|title=FusionGDB: fusion gene annotation DataBase|url=http://dx.doi.org/10.1093/nar/gky1067|journal=Nucleic Acids Research|volume=47|issue=D1|pages=D994–D1004|doi=10.1093/nar/gky1067|issn=0305-1048}}</ref>
|''KIAA1549::BRAF''<ref name=":6" /><ref name=":8">{{Cite journal|last=Appay|first=Romain|last2=Fina|first2=Frédéric|last3=Macagno|first3=Nicolas|last4=Padovani|first4=Laëtitia|last5=Colin|first5=Carole|last6=Barets|first6=Doriane|last7=Ordioni|first7=Joanna|last8=Scavarda|first8=Didier|last9=Giangaspero|first9=Felice|date=2018-10|title=Duplications of KIAA1549 and BRAF screening by Droplet Digital PCR from formalin-fixed paraffin-embedded DNA is an accurate alternative for KIAA1549-BRAF fusion detection in pilocytic astrocytomas|url=https://pubmed.ncbi.nlm.nih.gov/29802359|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=31|issue=10|pages=1490–1501|doi=10.1038/s41379-018-0050-6|issn=1530-0285|pmid=29802359}}</ref>
|duplication
|16.7%<ref name=":8" />
|Yes<ref name=":0" /><ref name=":6" />
|No
|Yes<ref name=":9">{{Cite journal|last=Schreck|first=Karisa C.|last2=Grossman|first2=Stuart A.|last3=Pratilas|first3=Christine A.|date=2019-08-28|title=BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors|url=https://pubmed.ncbi.nlm.nih.gov/31466300|journal=Cancers|volume=11|issue=9|pages=E1262|doi=10.3390/cancers11091262|issn=2072-6694|pmc=6769482|pmid=31466300}}</ref>
| - also seen in PLNTY, ganglioglioma, and pilocytic astrocytoma; can distinguish by methylation signature<ref name=":0" />
- in-frame fusion<ref name=":6" />
|-
|t(8;8)(p11.23;p11.22)<ref name=":6" /><ref name=":7" />
|''FGFR1::TACC1''<ref name=":6" />
|inversion
|2.5% (1/40)<ref name=":6" />
|Unknown
|Unknown
|Unknown
| - in-frame fusion<ref name=":6" />
- no FDA-approved anti-FGFR therapy for ganglioglioma at present
|-
|t(10;10)(q26.13;q25.3)<ref name=":6" /><ref name=":7" />
|''FGFR2::KIAA1598''<ref name=":6" />
|deletion
|2.5% (1/40)<ref name=":6" />
|Unknown
|Unknown
|Unknown
| - in-frame fusion<ref name=":6" />
<br />
|-
|t(10;10) (q26.13;q24.3)<ref name=":6" /><ref name=":7" />
|''FGFR2::INA''<ref name=":6" />
|inversion
|2.5% (1/40)<ref name=":6" />
|Unknown
|Unknown
|Unknown
| - in-frame fusion<ref name=":6" />
<br />
|-
|t(3;3)(p14.3;p25.2)<ref name=":6" /><ref name=":7" />
|''ERC2::RAF1''<ref name=":6" />
|deletion
|2.5%(1/40)<ref name=":6" />
|Unknown
|Unknown
|Yes (potential)<ref name=":9" />
| - in-frame fusion<ref name=":6" />
<br />
|-
|-
|t(14;7)(q32.32;7q34)<ref name=":6" /><ref name=":7" />
|''CDC42BPB::BRAF''<ref name=":6" />
|translocation
|2.5% (1/40)<ref name=":6" />
|Unknown
|Unknown
|Yes (potential)<ref name=":9" />
| - in-frame fusion<ref name=":6" />
<br />
|-
|-
|EXAMPLE t(9;22)(q34;q11.2) || EXAMPLE 3'ABL1 / 5'BCR || EXAMPLE der(22) || EXAMPLE 5%
|t(7;7)(p15.3;q34)<ref name=":6" /><ref name=":7" />
|''KLHL7::BRAF''<ref name=":6" />
|inversion
|2.5% (1/40) <ref name=":6" />
<br />
|Unknown
|Unknown
|Yes (potential)<ref name=":9" />
| - in-frame fusion<ref name=":6" />
<br />
|-
|-
|EXAMPLE t(8;21)(q22;q22) || EXAMPLE 5'RUNX1 / 3'RUNXT1 || EXAMPLE der(8) || EXAMPLE 5%
|t(1;11)(q25.2;q14.1)<ref name=":6" /><ref name=":7" />
|}
|''ABL2::GAB2''<ref name=":6" />
|translocation
|2.5% (1/40)<ref name=":6" />
<br />
|Unknown
|Unknown
|Yes (potential)<ref name=":9" />
| - in-frame fusion<ref name=":6" />
<br />
|}
==Characteristic Chromosomal Aberrations / Patterns==
==Characteristic Chromosomal Aberrations / Patterns==
None
==Genomic Gain/Loss/LOH<ref name=":6" />==
{| class="wikitable"
|'''Chr # '''
|'''Gain/Loss/Amp/LOH'''
|'''Minimal Region Genomic Coordinates [Genome Build]'''
|'''Minimal Region Cytoband'''
|'''Diagnostic Significance (Yes, No or Unknown)'''
|'''Prognostic Significance'''
'''(Yes, No or Unknown) '''
|'''Therapeutic Significance'''
'''(Yes, No or Unknown)'''
|'''Notes'''
|-
|1
|loss
|Chr1:1- 248956422
<br />
|Chr1
|Unknown
|Unknown
|Unknown
| colspan="1" rowspan="20" |This constellation of chromosomal abnormalities was found in a case series of 40 gangliogliomas[8].
It is unknown if the abnormalities are either diagnostic, prognostic or therapeutic.
|-
|3
|gain
|Chr3:1- 198295559
<br />
|Chr3
|Unknown
|Unknown
|Unknown
|-
|4
|gain
|Chr4:1- 190214555
|Chr4
|Unknown
|Unknown
|Unknown
|-
|5
|gain
|Chr5:1- 181538259
|Chr5
|Unknown
|Unknown
|Unknown
|-
|6
|gain
|Chr6:1- 170805979
|Chr6
|Unknown
|Unknown
|Unknown
|-
|7
|gain
|Chr7:1- 159345973
|Chr7
|Unknown
|Unknown
|Unknown
|-
|8
|gain
|Chr8:1- 145138636
|Chr8
|Unknown
|Unknown
|Unknown
|-
|9
|gain
|Chr9:1- 138394717
|Chr9
|Unknown
|Unknown
|Unknown
|-
|10
|loss (segmental)
|Chr10:1- 133797422
|Chr10
|Unknown
|Unknown
|Unknown
|-
|11
|gain
|Chr11:1- 135086622
|Chr11
|Unknown
|Unknown
|Unknown
|-
|12
|gain
|Chr12:1- 133275309
|Chr12
|Unknown
|Unknown
|Unknown
|-
|15
|gain
|Chr15: 1- 101991189
|Chr15
|Unknown
|Unknown
|Unknown
|-
|16
|Gain
|Chr16:1-90338345
<br />
|Chr16
|Unknown
|Unknown
|Unknown
|-
|16
|loss
|Chr16:1-90338345
<br />
|Chr16
|Unknown
|Unknown
|Unknown
|-
|17
|loss
|Chr17:1- 83257441
|Chr17
|Unknown
|Unknown
|Unknown
|-
|18
|gain
|Chr18:1- 80373285
|Chr18
|Unknown
|Unknown
|Unknown
|-
|19
|gain
|Chr19:1- 58617616
|Chr19
|Unknown
|Unknown
|Unknown
|-
|-
|20
|gain
|Chr20:1- 64444167
|Chr20
|Unknown
|Unknown
|Unknown
|-
|-
|EXAMPLE 8 || EXAMPLE Gain || EXAMPLE chr8:0-1000000
|21
|gain
|Chr21:1- 46709983
|Chr21
|Unknown
|Unknown
|Unknown
|-
|-
|EXAMPLE 7 || EXAMPLE Loss || EXAMPLE chr7:0-1000000
|22
|}
|gain
|Chr22:1- 50818468
|Chr22
|Unknown
|Unknown
|Unknown
|}
<br />
==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
{| class="wikitable"
|'''Gene; Genetic Alteration'''
|'''Presumed Mechanism (Tumor Suppressor Gene (TSG)/Oncogene/Other)'''
|'''Prevalence (COSMIC/ TCGA/Other)'''
|'''Concomitant Mutations'''
|'''Mutually Exclusive Mutations'''
|'''Diagnostic Significance (Yes, No or Unknown)'''
|'''Prognostic Significance'''
'''(Yes, No or Unknown) '''
|'''Therapeutic Significance'''
'''(Yes, No or Unknown)'''
|'''Notes'''
|-
|-
|''BRAF'' p.V600E<ref name=":0" /><ref name=":6" />
|-
|oncogene
| EXAMPLE TP53 || EXAMPLE R273H || EXAMPLE Tumor Suppressor || EXAMPLE LOF || EXAMPLE 20%
|10-60%<ref name=":0" />
|}
|Homozygous deletion of CDKN2A<ref name=":6" />[8]
===Other Mutations===
H3-3A p.K27M<ref>{{Cite journal|last=Pagès|first=Mélanie|last2=Beccaria|first2=Kevin|last3=Boddaert|first3=Nathalie|last4=Saffroy|first4=Raphaël|last5=Besnard|first5=Aurore|last6=Castel|first6=David|last7=Fina|first7=Frédéric|last8=Barets|first8=Doriane|last9=Barret|first9=Emilie|date=2018-01|title=Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma|url=https://pubmed.ncbi.nlm.nih.gov/27984673|journal=Brain Pathology (Zurich, Switzerland)|volume=28|issue=1|pages=103–111|doi=10.1111/bpa.12473|issn=1750-3639|pmc=8028391|pmid=27984673}}</ref>
|''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" />
|Yes<ref name=":0" /><ref name=":6" />
|Yes<ref name=":10">{{Cite journal|last=Ryall|first=Scott|last2=Zapotocky|first2=Michal|last3=Fukuoka|first3=Kohei|last4=Nobre|first4=Liana|last5=Guerreiro Stucklin|first5=Ana|last6=Bennett|first6=Julie|last7=Siddaway|first7=Robert|last8=Li|first8=Christopher|last9=Pajovic|first9=Sanja|date=2020-04-13|title=Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas|url=https://pubmed.ncbi.nlm.nih.gov/32289278|journal=Cancer Cell|volume=37|issue=4|pages=569–583.e5|doi=10.1016/j.ccell.2020.03.011|issn=1878-3686|pmc=7169997|pmid=32289278}}</ref>
|Yes<ref name=":11">{{Cite journal|last=Kowalewski|first=Adam|last2=Durślewicz|first2=Justyna|last3=Zdrenka|first3=Marek|last4=Grzanka|first4=Dariusz|last5=Szylberg|first5=Łukasz|date=2020-08|title=Clinical Relevance of BRAF V600E Mutation Status in Brain Tumors with a Focus on a Novel Management Algorithm|url=https://pubmed.ncbi.nlm.nih.gov/32648041|journal=Targeted Oncology|volume=15|issue=4|pages=531–540|doi=10.1007/s11523-020-00735-9|issn=1776-260X|pmc=7434793|pmid=32648041}}</ref>
|FDA-approved therapy includes dabrafenib-trametinib<ref name=":11" />
<br />
|-
|-
|''BRAF'' indel events: p.L505delinsLEYLS p.R506delinsRVLR p.R506delinsRSTQ p.T599_W604delinsTDG) <ref name=":6" />
|oncogene
|10%<ref name=":6" />
|
|''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" />
|Yes<ref name=":0" /><ref name=":6" />
|Unknown
|Unknown
|
|-
|-
| Concomitant Mutations || EXAMPLE IDH1 R123H
|''KRAS'' p.Q61K<ref name=":6" />
|oncogene
|5%<ref name=":6" />
|
|''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" />
|Yes<ref name=":0" /><ref name=":6" />
|No<ref name=":6" /><ref name=":10" />
|No
|
|-
|-
| Secondary Mutations || EXAMPLE Trisomy 7
|''FGFR2'' exon 17 splicesite mutation<ref name=":6" />
|oncogene
|2.5%<ref name=":6" />
<br />
|
|''KRAS, RAF1, NF1, FGFR1, and BRAF''<ref name=":6" />
|Yes<ref name=":0" /><ref name=":6" />
|No<ref name=":6" /><ref name=":10" />
|No
|<nowiki>- no FDA-approved anti-FGFR therapy for ganglioglioma at present </nowiki>
<br />
|-
|-
|Mutually Exclusive || EXAMPLE EGFR Amplification
|''FGFR1'' p.N546K<ref name=":6" />
|oncogene
|2.5%<ref name=":6" />
<br />
|
|''KRAS, RAF1,''
'' NF1, BRAF, and FGFR2''<ref name=":6" />
|Yes<ref name=":0" /><ref name=":6" />
|No<ref name=":6" /><ref name=":10" />
|No
|<nowiki>- no FDA-approved anti-FGFR therapy for ganglioglioma at present </nowiki>
<br />
|}
|}
==Epigenomics (Methylation)==
==Epigenomics (Methylation)==
Methylation profiling can be used in the diagnosis of ganglioglioma, however low tumour cellularity can impact on feasibility in the diagnostic setting<ref name=":0" />.
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
90% of gangliogliomas harbor genetic alterations activating the MAPK signaling pathway, with non-MAPK signaling seen in 10% of cases (e.g. ''ABL2::GAB2'' gene fusion)<ref name=":6" />.
{| class="wikitable"
|'''Gene; Genetic Alteration'''
|'''Pathway'''
|'''Pathophysiologic Outcome'''
|-
|BRAF; activating alterations
|MAPK signaling
|Increased cell growth and proliferation
|-
|RAF1; activating alterations
|MAPK signaling
|Increase cell growth and proliferation
|-
|KRAS; activating mutations
|MAPK signaling
|Increase cell growth and proliferation
|-
|NF1; inactivating mutations
|MAPK signaling
|Increase cell growth and proliferation
|-
|FGFR1/2/3; activating alterations
|MAPK signaling
|Increase cell growth and proliferation
|}
==Diagnostic Testing Methods==
==Diagnostic Testing Methods==
*Chromosome microarray
*Next generation sequencing
*DNA methylation profiling
==Familial Forms==
==Familial Forms==
Inactivating germline mutations or deletions of ''NF1'', as occurs in neurofibromatosis type 1, can be associated with a minor proportion of gangliogliomas<ref name=":6" /><ref>{{Cite journal|last=Rodriguez|first=Fausto J.|last2=Perry|first2=Arie|last3=Gutmann|first3=David H.|last4=O'Neill|first4=Brian Patrick|last5=Leonard|first5=Jeffrey|last6=Bryant|first6=Sandra|last7=Giannini|first7=Caterina|date=2008-03|title=Gliomas in neurofibromatosis type 1: a clinicopathologic study of 100 patients|url=https://pubmed.ncbi.nlm.nih.gov/18344915|journal=Journal of Neuropathology and Experimental Neurology|volume=67|issue=3|pages=240–249|doi=10.1097/NEN.0b013e318165eb75|issn=0022-3069|pmc=3417064|pmid=18344915}}</ref>
==Other Information==
==Links==
==Links==
==References==
==References==
<references />