CNS5:Diffuse leptomeningeal glioneuronal tumour: Difference between revisions

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{{Under Construction}}
{{DISPLAYTITLE:Diffuse leptomeningeal glioneuronal tumour}}
==Primary Author(s)*==


Put your text here (Example: Jane Smith, PhD, Institute of Genomics)
[[CNS5:Table_of_Contents|Central Nervous System Tumours (WHO Classification, 5th ed.)]]


__TOC__
{{Under Construction}}


==Cancer Category/Type==
<br />
==Primary Author(s)*==


Put your text here


==Cancer Sub-Classification / Subtype==
Laveniya Satgunaseelan, MBBS BMedSc FRCPA, Royal Prince Alfred Hospital
==WHO Classification of Disease==


Put your text here
{| class="wikitable"
!Structure
!Disease
|-
|Book
|Central Nervous System Tumours (5th ed.)
|-
|Category
|Gliomas, glioneuronal tumours, and neuronal tumours
|-
|Family
|Gliomas, glioneuronal tumours, and neuronal tumours
|-
|Type
|Glioneuronal and neuronal tumours
|-
|Subtype(s)
|Diffuse leptomeningeal glioneuronal tumour
|}


==Definition / Description of Disease==
==Related Terminology==


Put your text here
{| class="wikitable"
 
|+
==Synonyms / Terminology==
|Acceptable
 
|N/A
Put your text here
|-
 
|Not Recommended
==Epidemiology / Prevalence==
|Disseminated oligodendroglioma-like leptomeningeal neoplasm; primary leptomeningeal oligodendrogliomatosis
 
|}
Put your text here
 
==Clinical Features==
 
Put your text here
 
==Sites of Involvement==
 
Put your text here
 
==Morphologic Features==
 
Put your text here
 
==Immunophenotype==
 
Put your text here and/or fill in the table


==Gene Rearrangements==
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|Positive (universal)||EXAMPLE CD1
|''BRAF''
|''KIAA1549::BRAF''
|Tandem duplication at chr7q34 - duplication and insertion of ~2Mb  fragment resulting in fusion of 5’ of ''KIAA1549'' with 3’ of ''BRAF''||t(7;7)(q34;q34)
|Common (72%; WHO)
|D, T
|Yes (WHO)
|Case report evidence of efficacy of BRAF inhibitors in DLGNT case  harboring ''KIAA1549::BRAF'' fusion<ref>{{Cite journal|last=Valiakhmetova|first=Andge|last2=Papusha|first2=Ludmila|last3=Yasko|first3=Ludmila|last4=Druy|first4=Alexander|last5=Karachunsky|first5=Alexander|last6=Novichkova|first6=Galina|last7=Hwang|first7=Eugene I|last8=Packer|first8=Roger J|date=2020-12-04|title=LGG-26. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT) IN CHILDREN: DIFFERENT CLINICAL PRESENTATIONS AND OUTCOMES|url=https://academic.oup.com/neuro-oncology/article/22/Supplement_3/iii371/6018960|journal=Neuro-Oncology|language=en|volume=22|issue=Supplement_3|pages=iii371–iii371|doi=10.1093/neuonc/noaa222.408|issn=1522-8517|pmc=7715974}}</ref>
|-
|-
|Positive (subset)||EXAMPLE CD2
|''NTRK1/2/3''
|Fusion partner not specified (PMID: 29766299)
|Downstream activation of MAPK/ERK signalling pathway  in CNS tumors
|Not specified
|Rare
|D,T
|Yes (WHO)
|3 cases with ''NTRK1/2/3'' fusions<ref>{{Cite journal|last=Deng|first=Maximilian Y.|last2=Sill|first2=Martin|last3=Chiang|first3=Jason|last4=Schittenhelm|first4=Jens|last5=Ebinger|first5=Martin|last6=Schuhmann|first6=Martin U.|last7=Monoranu|first7=Camelia-Maria|last8=Milde|first8=Till|last9=Wittmann|first9=Andrea|date=2018-08|title=Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features|url=https://pubmed.ncbi.nlm.nih.gov/29766299|journal=Acta Neuropathologica|volume=136|issue=2|pages=239–253|doi=10.1007/s00401-018-1865-4|issn=1432-0533|pmid=29766299}}</ref>
|-
|-
|Negative (universal)||EXAMPLE CD3
|''RAF1''
|''TRIM33:RAF1''
|Downstream activation of MAPK/ERK signalling  pathway in CNS tumors
|t(1;3)(p13;p25)
|Rare
|D
|Yes (WHO)
|1 case with ''TRIM33::RAF1'' fusion<ref>{{Cite journal|last=Deng|first=Maximilian Y.|last2=Sill|first2=Martin|last3=Chiang|first3=Jason|last4=Schittenhelm|first4=Jens|last5=Ebinger|first5=Martin|last6=Schuhmann|first6=Martin U.|last7=Monoranu|first7=Camelia-Maria|last8=Milde|first8=Till|last9=Wittmann|first9=Andrea|date=2018-08|title=Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features|url=https://pubmed.ncbi.nlm.nih.gov/29766299|journal=Acta Neuropathologica|volume=136|issue=2|pages=239–253|doi=10.1007/s00401-018-1865-4|issn=1432-0533|pmid=29766299}}</ref>
|-
|-
|Negative (subset)||EXAMPLE CD4
| colspan="8" |
|}
|}


==Chromosomal Rearrangements (Gene Fusions)==
Put your text here and/or fill in the table


==Individual Region Genomic Gain/Loss/LOH==
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
!
|-
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 5%
|1p
|Loss
|Complete arm loss (PMIDs: 22941225, 29766299)
|Chr1p
|Unknown
|D
|Yes (WHO)
|Prevalence common, between 59% (by FISH; PMIDs: 22596013,  17184079, 19486008, 22941225, 25720745) and 100% (by CNV calling from DNA methylation  array data<ref>{{Cite journal|last=Deng|first=Maximilian Y.|last2=Sill|first2=Martin|last3=Chiang|first3=Jason|last4=Schittenhelm|first4=Jens|last5=Ebinger|first5=Martin|last6=Schuhmann|first6=Martin U.|last7=Monoranu|first7=Camelia-Maria|last8=Milde|first8=Till|last9=Wittmann|first9=Andrea|date=2018-08|title=Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features|url=https://pubmed.ncbi.nlm.nih.gov/29766299|journal=Acta Neuropathologica|volume=136|issue=2|pages=239–253|doi=10.1007/s00401-018-1865-4|issn=1432-0533|pmid=29766299}}</ref>).
|-
|-
|EXAMPLE t(8;21)(q22;q22)||EXAMPLE 5'RUNX1 / 3'RUNXT1||EXAMPLE der(8)||EXAMPLE 5%
|1q
|}
|Gain
|Complete arm gain (PMIDs: 29766299, 30465258)
==Characteristic Chromosomal Aberrations / Patterns==
|Chr1q
|Unknown
|D
|Yes (WHO)
|Prevalence common, between 56% and 63% (by CNV calling from DNA methylation  array data<ref>{{Cite journal|last=Deng|first=Maximilian Y.|last2=Sill|first2=Martin|last3=Chiang|first3=Jason|last4=Schittenhelm|first4=Jens|last5=Ebinger|first5=Martin|last6=Schuhmann|first6=Martin U.|last7=Monoranu|first7=Camelia-Maria|last8=Milde|first8=Till|last9=Wittmann|first9=Andrea|date=2018-08|title=Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features|url=https://pubmed.ncbi.nlm.nih.gov/29766299|journal=Acta Neuropathologica|volume=136|issue=2|pages=239–253|doi=10.1007/s00401-018-1865-4|issn=1432-0533|pmid=29766299}}</ref><ref>{{Cite journal|last=Chiang|first=Jason|last2=Dalton|first2=James|last3=Upadhyaya|first3=Santhosh A.|last4=Patay|first4=Zoltán|last5=Qaddoumi|first5=Ibrahim|last6=Li|first6=Xiaoyu|last7=Segura|first7=Annette D.|last8=Sharma|first8=Suash|last9=Ismail|first9=Azzam|date=2019-01|title=Chromosome arm 1q gain is an adverse prognostic factor in localized and diffuse leptomeningeal glioneuronal tumors with BRAF gene fusion and 1p deletion|url=https://pubmed.ncbi.nlm.nih.gov/30465258|journal=Acta Neuropathologica|volume=137|issue=1|pages=179–181|doi=10.1007/s00401-018-1940-x|issn=1432-0533|pmid=30465258}}</ref>)


Put your text here
Found in all cases of DLGNT methylation class (MC)-2<ref>{{Cite journal|last=Deng|first=Maximilian Y.|last2=Sill|first2=Martin|last3=Chiang|first3=Jason|last4=Schittenhelm|first4=Jens|last5=Ebinger|first5=Martin|last6=Schuhmann|first6=Martin U.|last7=Monoranu|first7=Camelia-Maria|last8=Milde|first8=Till|last9=Wittmann|first9=Andrea|date=2018-08|title=Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features|url=https://pubmed.ncbi.nlm.nih.gov/29766299|journal=Acta Neuropathologica|volume=136|issue=2|pages=239–253|doi=10.1007/s00401-018-1865-4|issn=1432-0533|pmid=29766299}}</ref>
 
|-
==Genomic Gain/Loss/LOH==
| colspan="8" |
 
|}
Put your text here and/or fill in the table


==Characteristic Chromosomal or Other Global Mutational Patterns==
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
!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
|-
|-
|EXAMPLE 8||EXAMPLE Gain||EXAMPLE chr8:0-1000000
|Co-deletion of  1p and 19q
|Unknown
|Recurrent to common
|D
|Yes  (WHO)
|Prevalence  between 18% and 33%<ref>{{Cite journal|last=Rodriguez|first=Fausto J.|last2=Schniederjan|first2=Matthew J.|last3=Nicolaides|first3=Theo|last4=Tihan|first4=Tarik|last5=Burger|first5=Peter C.|last6=Perry|first6=Arie|date=2015-04|title=High rate of concurrent BRAF-KIAA1549 gene fusion and 1p deletion in disseminated oligodendroglioma-like leptomeningeal neoplasms (DOLN)|url=https://pubmed.ncbi.nlm.nih.gov/25720745|journal=Acta Neuropathologica|volume=129|issue=4|pages=609–610|doi=10.1007/s00401-015-1400-9|issn=1432-0533|pmc=4696044|pmid=25720745}}</ref><ref>{{Cite journal|last=Deng|first=Maximilian Y.|last2=Sill|first2=Martin|last3=Chiang|first3=Jason|last4=Schittenhelm|first4=Jens|last5=Ebinger|first5=Martin|last6=Schuhmann|first6=Martin U.|last7=Monoranu|first7=Camelia-Maria|last8=Milde|first8=Till|last9=Wittmann|first9=Andrea|date=2018-08|title=Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features|url=https://pubmed.ncbi.nlm.nih.gov/29766299|journal=Acta Neuropathologica|volume=136|issue=2|pages=239–253|doi=10.1007/s00401-018-1865-4|issn=1432-0533|pmid=29766299}}</ref>
|-
|-
|EXAMPLE 7||EXAMPLE Loss||EXAMPLE chr7:0-1000000
| colspan="6" |
|}
|}
 
==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
Put your text here and/or fill in the tables
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
!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
|-
|-
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
|''BRAF''
|}
|p.V600E (activating mutation)
|Oncogene
===Other Mutations===
<br />
|Rare
|D, T
|Yes (WHO, NCCN)
|Rare reports  of DLGNTs harboring ''BRAF'' p.V600E mutations\<ref>{{Cite journal|last=Dodgshun|first=Andrew J.|last2=SantaCruz|first2=Nadine|last3=Hwang|first3=Jaeho|last4=Ramkissoon|first4=Shakti H.|last5=Malkin|first5=Hayley|last6=Bergthold|first6=Guillaume|last7=Manley|first7=Peter|last8=Chi|first8=Susan|last9=MacGregor|first9=Duncan|date=2016-06|title=Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation|url=https://pubmed.ncbi.nlm.nih.gov/26994902|journal=Journal of Neuro-Oncology|volume=128|issue=2|pages=293–302|doi=10.1007/s11060-016-2109-x|issn=1573-7373|pmid=26994902}}</ref><ref>{{Cite journal|last=Appay|first=Romain|last2=Pages|first2=Mélanie|last3=Colin|first3=Carole|last4=Jones|first4=David T. W.|last5=Varlet|first5=Pascale|last6=Figarella-Branger|first6=Dominique|date=2020-06-30|title=Diffuse leptomeningeal glioneuronal tumor: a double misnomer? A report of two cases|url=https://pubmed.ncbi.nlm.nih.gov/32605662|journal=Acta Neuropathologica Communications|volume=8|issue=1|pages=95|doi=10.1186/s40478-020-00978-7|issn=2051-5960|pmc=7325675|pmid=32605662}}</ref>, including abstracts detailing efficacy of BRAF inhibtors in ''BRAF''-mutant  DLGNT<ref>{{Cite journal|last=Valiakhmetova|first=Andge|last2=Papusha|first2=Ludmila|last3=Yasko|first3=Ludmila|last4=Druy|first4=Alexander|last5=Karachunsky|first5=Alexander|last6=Novichkova|first6=Galina|last7=Hwang|first7=Eugene I|last8=Packer|first8=Roger J|date=2020-12-04|title=LGG-26. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT) IN CHILDREN: DIFFERENT CLINICAL PRESENTATIONS AND OUTCOMES|url=https://academic.oup.com/neuro-oncology/article/22/Supplement_3/iii371/6018960|journal=Neuro-Oncology|language=en|volume=22|issue=Supplement_3|pages=iii371–iii371|doi=10.1093/neuonc/noaa222.408|issn=1522-8517|pmc=7715974}}</ref><ref>{{Cite journal|last=Aung|first=Le Le|date=2020-12-01|title=HGG-06. REMARKABLE RESPONSE TO BRAF INHIBITOR IN AN INFANT WITH DISSEMINATED DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT)|url=https://doi.org/10.1093/neuonc/noaa222.297|journal=Neuro-Oncology|volume=22|issue=Supplement_3|pages=iii345|doi=10.1093/neuonc/noaa222.297|issn=1522-8517|pmc=7715114}}</ref>)
<br />
|-
|''PIK3CA''
|p.E545A
|Oncogene
<br />
|Rare
|Nil
|No
|Case report of co-occurring ''PIK3CA'' variant<ref>{{Cite journal|last=Appay|first=Romain|last2=Pages|first2=Mélanie|last3=Colin|first3=Carole|last4=Jones|first4=David T. W.|last5=Varlet|first5=Pascale|last6=Figarella-Branger|first6=Dominique|date=2020-06-30|title=Diffuse leptomeningeal glioneuronal tumor: a double misnomer? A report of two cases|url=https://pubmed.ncbi.nlm.nih.gov/32605662|journal=Acta Neuropathologica Communications|volume=8|issue=1|pages=95|doi=10.1186/s40478-020-00978-7|issn=2051-5960|pmc=7325675|pmid=32605662}}</ref>
|-
|''TERT''
|Activating mutations in promoter region
|Oncogene
|Rare
|Nil
|No
|Point mutations described include C228T and  C228A<ref>{{Cite journal|last=Deng|first=Maximilian Y.|last2=Sill|first2=Martin|last3=Chiang|first3=Jason|last4=Schittenhelm|first4=Jens|last5=Ebinger|first5=Martin|last6=Schuhmann|first6=Martin U.|last7=Monoranu|first7=Camelia-Maria|last8=Milde|first8=Till|last9=Wittmann|first9=Andrea|date=2018-08|title=Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features|url=https://pubmed.ncbi.nlm.nih.gov/29766299|journal=Acta Neuropathologica|volume=136|issue=2|pages=239–253|doi=10.1007/s00401-018-1865-4|issn=1432-0533|pmid=29766299}}</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.
==Epigenomic Alterations==
 
On methylation profiling of a large series of DLGNTs, two methylation classes have been defined - DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2. All cases of DLGNT-MC-2 exhibited gain of chr1q, with 1p/19q codeletion more common in DLGNT-MC-1<ref>{{Cite journal|last=Deng|first=Maximilian Y.|last2=Sill|first2=Martin|last3=Chiang|first3=Jason|last4=Schittenhelm|first4=Jens|last5=Ebinger|first5=Martin|last6=Schuhmann|first6=Martin U.|last7=Monoranu|first7=Camelia-Maria|last8=Milde|first8=Till|last9=Wittmann|first9=Andrea|date=2018-08|title=Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features|url=https://pubmed.ncbi.nlm.nih.gov/29766299|journal=Acta Neuropathologica|volume=136|issue=2|pages=239–253|doi=10.1007/s00401-018-1865-4|issn=1432-0533|pmid=29766299}}</ref>.
==Genes and Main Pathways Involved==
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Type!!Gene/Region/Other
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|Concomitant Mutations||EXAMPLE IDH1 R123H
|''BRAF,  FGFR1''; Activating mutations
|MAPK signaling
|Increased  cell growth and proliferation
|-
|-
|Secondary Mutations||EXAMPLE Trisomy 7
|''FGFR1,  PIK3CA''; Activating mutations
|PI3K–Akt  signaling pathway
|Increased  cell growth, proliferation, survival and motility
|-
|-
|Mutually Exclusive||EXAMPLE EGFR Amplification
| colspan="3" |
|}
|}
==Genetic Diagnostic Testing Methods==


==Epigenomics (Methylation)==
-         Fusion detection via targeted NGS (RNA or DNA panels) or FISH
 
Put your text here
 
==Genes and Main Pathways Involved==
 
Put your text here


==Diagnostic Testing Methods==
-         Chromosomal alterations can be detected by FISH, SNP array, methylation array or NGS


Put your text here
-         Methylation profiling via CNS tumor classifiers for DLGNT-MCs
 
==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==
 
Diagnosis: Put your text here
 
Prognosis: Put your text here
 
Therapeutic: Put your text here


==Familial Forms==
==Familial Forms==


Put your text here
One case of DLGNT in which a germline mutation in ''RAF1'' has been documented<ref>{{Cite journal|last=Dodgshun|first=Andrew J.|last2=SantaCruz|first2=Nadine|last3=Hwang|first3=Jaeho|last4=Ramkissoon|first4=Shakti H.|last5=Malkin|first5=Hayley|last6=Bergthold|first6=Guillaume|last7=Manley|first7=Peter|last8=Chi|first8=Susan|last9=MacGregor|first9=Duncan|date=2016-06|title=Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation|url=https://pubmed.ncbi.nlm.nih.gov/26994902|journal=Journal of Neuro-Oncology|volume=128|issue=2|pages=293–302|doi=10.1007/s11060-016-2109-x|issn=1573-7373|pmid=26994902}}</ref>.
 
==Other Information==
 
Put your text here
 
==Links==
 
Put your links here (use "Link" icon at top of page)


<br />
==References==
==References==
(use "Cite" icon at top of page)
[[Category:CNS5]]
[[Category:DISEASE]]
[[Category:Diseases D]]
<references />
<references />
===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==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

Latest revision as of 22:00, 7 July 2025


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


Primary Author(s)*

Laveniya Satgunaseelan, MBBS BMedSc FRCPA, Royal Prince Alfred Hospital

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 Glioneuronal and neuronal tumours
Subtype(s) Diffuse leptomeningeal glioneuronal tumour

Related Terminology

Acceptable N/A
Not Recommended Disseminated oligodendroglioma-like leptomeningeal neoplasm; primary leptomeningeal oligodendrogliomatosis

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
BRAF KIAA1549::BRAF Tandem duplication at chr7q34 - duplication and insertion of ~2Mb fragment resulting in fusion of 5’ of KIAA1549 with 3’ of BRAF t(7;7)(q34;q34) Common (72%; WHO) D, T Yes (WHO) Case report evidence of efficacy of BRAF inhibitors in DLGNT case harboring KIAA1549::BRAF fusion[1]
NTRK1/2/3 Fusion partner not specified (PMID: 29766299) Downstream activation of MAPK/ERK signalling pathway in CNS tumors Not specified Rare D,T Yes (WHO) 3 cases with NTRK1/2/3 fusions[2]
RAF1 TRIM33:RAF1 Downstream activation of MAPK/ERK signalling pathway in CNS tumors t(1;3)(p13;p25) Rare D Yes (WHO) 1 case with TRIM33::RAF1 fusion[3]


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
1p Loss Complete arm loss (PMIDs: 22941225, 29766299) Chr1p Unknown D Yes (WHO) Prevalence common, between 59% (by FISH; PMIDs: 22596013, 17184079, 19486008, 22941225, 25720745) and 100% (by CNV calling from DNA methylation array data[4]).
1q Gain Complete arm gain (PMIDs: 29766299, 30465258) Chr1q Unknown D Yes (WHO) Prevalence common, between 56% and 63% (by CNV calling from DNA methylation array data[5][6])

Found in all cases of DLGNT methylation class (MC)-2[7]

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
Co-deletion of 1p and 19q Unknown Recurrent to common D Yes (WHO) Prevalence between 18% and 33%[8][9]

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
BRAF p.V600E (activating mutation) Oncogene


Rare D, T Yes (WHO, NCCN) Rare reports of DLGNTs harboring BRAF p.V600E mutations\[10][11], including abstracts detailing efficacy of BRAF inhibtors in BRAF-mutant DLGNT[12][13])


PIK3CA p.E545A Oncogene


Rare Nil No Case report of co-occurring PIK3CA variant[14]
TERT Activating mutations in promoter region Oncogene Rare Nil No Point mutations described include C228T and C228A[15]

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

On methylation profiling of a large series of DLGNTs, two methylation classes have been defined - DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2. All cases of DLGNT-MC-2 exhibited gain of chr1q, with 1p/19q codeletion more common in DLGNT-MC-1[16].

Genes and Main Pathways Involved

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
BRAF, FGFR1; Activating mutations MAPK signaling Increased cell growth and proliferation
FGFR1, PIK3CA; Activating mutations PI3K–Akt signaling pathway Increased cell growth, proliferation, survival and motility

Genetic Diagnostic Testing Methods

-         Fusion detection via targeted NGS (RNA or DNA panels) or FISH

-         Chromosomal alterations can be detected by FISH, SNP array, methylation array or NGS

-         Methylation profiling via CNS tumor classifiers for DLGNT-MCs

Familial Forms

One case of DLGNT in which a germline mutation in RAF1 has been documented[17].


References

  1. ↑ Valiakhmetova, Andge; et al. (2020-12-04). "LGG-26. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT) IN CHILDREN: DIFFERENT CLINICAL PRESENTATIONS AND OUTCOMES". Neuro-Oncology. 22 (Supplement_3): iii371–iii371. doi:10.1093/neuonc/noaa222.408. ISSN 1522-8517. PMC 7715974 Check |pmc= value (help).
  2. ↑ Deng, Maximilian Y.; et al. (2018-08). "Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features". Acta Neuropathologica. 136 (2): 239–253. doi:10.1007/s00401-018-1865-4. ISSN 1432-0533. PMID 29766299. Check date values in: |date= (help)
  3. ↑ Deng, Maximilian Y.; et al. (2018-08). "Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features". Acta Neuropathologica. 136 (2): 239–253. doi:10.1007/s00401-018-1865-4. ISSN 1432-0533. PMID 29766299. Check date values in: |date= (help)
  4. ↑ Deng, Maximilian Y.; et al. (2018-08). "Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features". Acta Neuropathologica. 136 (2): 239–253. doi:10.1007/s00401-018-1865-4. ISSN 1432-0533. PMID 29766299. Check date values in: |date= (help)
  5. ↑ Deng, Maximilian Y.; et al. (2018-08). "Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features". Acta Neuropathologica. 136 (2): 239–253. doi:10.1007/s00401-018-1865-4. ISSN 1432-0533. PMID 29766299. Check date values in: |date= (help)
  6. ↑ Chiang, Jason; et al. (2019-01). "Chromosome arm 1q gain is an adverse prognostic factor in localized and diffuse leptomeningeal glioneuronal tumors with BRAF gene fusion and 1p deletion". Acta Neuropathologica. 137 (1): 179–181. doi:10.1007/s00401-018-1940-x. ISSN 1432-0533. PMID 30465258. Check date values in: |date= (help)
  7. ↑ Deng, Maximilian Y.; et al. (2018-08). "Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features". Acta Neuropathologica. 136 (2): 239–253. doi:10.1007/s00401-018-1865-4. ISSN 1432-0533. PMID 29766299. Check date values in: |date= (help)
  8. ↑ Rodriguez, Fausto J.; et al. (2015-04). "High rate of concurrent BRAF-KIAA1549 gene fusion and 1p deletion in disseminated oligodendroglioma-like leptomeningeal neoplasms (DOLN)". Acta Neuropathologica. 129 (4): 609–610. doi:10.1007/s00401-015-1400-9. ISSN 1432-0533. PMC 4696044. PMID 25720745. Check date values in: |date= (help)
  9. ↑ Deng, Maximilian Y.; et al. (2018-08). "Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features". Acta Neuropathologica. 136 (2): 239–253. doi:10.1007/s00401-018-1865-4. ISSN 1432-0533. PMID 29766299. Check date values in: |date= (help)
  10. ↑ Dodgshun, Andrew J.; et al. (2016-06). "Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation". Journal of Neuro-Oncology. 128 (2): 293–302. doi:10.1007/s11060-016-2109-x. ISSN 1573-7373. PMID 26994902. Check date values in: |date= (help)
  11. ↑ Appay, Romain; et al. (2020-06-30). "Diffuse leptomeningeal glioneuronal tumor: a double misnomer? A report of two cases". Acta Neuropathologica Communications. 8 (1): 95. doi:10.1186/s40478-020-00978-7. ISSN 2051-5960. PMC 7325675 Check |pmc= value (help). PMID 32605662 Check |pmid= value (help).
  12. ↑ Valiakhmetova, Andge; et al. (2020-12-04). "LGG-26. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT) IN CHILDREN: DIFFERENT CLINICAL PRESENTATIONS AND OUTCOMES". Neuro-Oncology. 22 (Supplement_3): iii371–iii371. doi:10.1093/neuonc/noaa222.408. ISSN 1522-8517. PMC 7715974 Check |pmc= value (help).
  13. ↑ Aung, Le Le (2020-12-01). "HGG-06. REMARKABLE RESPONSE TO BRAF INHIBITOR IN AN INFANT WITH DISSEMINATED DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT)". Neuro-Oncology. 22 (Supplement_3): iii345. doi:10.1093/neuonc/noaa222.297. ISSN 1522-8517. PMC 7715114 Check |pmc= value (help).
  14. ↑ Appay, Romain; et al. (2020-06-30). "Diffuse leptomeningeal glioneuronal tumor: a double misnomer? A report of two cases". Acta Neuropathologica Communications. 8 (1): 95. doi:10.1186/s40478-020-00978-7. ISSN 2051-5960. PMC 7325675 Check |pmc= value (help). PMID 32605662 Check |pmid= value (help).
  15. ↑ Deng, Maximilian Y.; et al. (2018-08). "Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features". Acta Neuropathologica. 136 (2): 239–253. doi:10.1007/s00401-018-1865-4. ISSN 1432-0533. PMID 29766299. Check date values in: |date= (help)
  16. ↑ Deng, Maximilian Y.; et al. (2018-08). "Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features". Acta Neuropathologica. 136 (2): 239–253. doi:10.1007/s00401-018-1865-4. ISSN 1432-0533. PMID 29766299. Check date values in: |date= (help)
  17. ↑ Dodgshun, Andrew J.; et al. (2016-06). "Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation". Journal of Neuro-Oncology. 128 (2): 293–302. doi:10.1007/s11060-016-2109-x. ISSN 1573-7373. PMID 26994902. Check date values in: |date= (help)
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