CNS5:Diffuse leptomeningeal glioneuronal tumour

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

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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

WHO Essential and Desirable Genetic Diagnostic Criteria

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WHO Essential Criteria (Genetics)*
WHO Desirable Criteria (Genetics)*
Other Classification

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

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 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
NTRK1/2/3	Fusion partner not specified (PMID: 29766299) BRAF	Downstream activation of MAPK/ERK signalling pathway in CNS tumors	Not specified	Rare	D,T	Yes (WHO)	3 cases with NTRK1/2/3 fusions
RAF1BRAF	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

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; PMID: 29766299).
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; PMIDs: 29766299, 30465258) Found in all cases of DLGNT methylation class (MC)-2 (PMID: 29766299)

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% (PMIDs: 25720745, 29766299)

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 (PMIDs: 26994902, 32605662), including abstracts detailing efficacy of BRAF inhibtors in BRAF-mutant DLGNT (PMCID: PMC7715974; https://doi.org/10.1093/neuonc/noaa222.297)
FGFR1	p.N456K	Oncogene	Rare	D	Yes (WHO)	PMID: 27061725
PIK3CA	p.E545A	Oncogene	Rare	Nil	No	PMID: 32605662
TERT	Activating mutations in promoter region	Oncogene	Rare	Nil	No	Point mutations described include C228T and C228A (PMID: 29766299)

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 (PMID: 29766299).

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 (PMID: 26994902).

Additional Information

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Links

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References

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Notes

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Prior Author(s): *Citation of this Page: “Diffuse leptomeningeal glioneuronal tumour”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 06/28/2025, https://ccga.io/index.php/CNS5:Diffuse leptomeningeal glioneuronal tumour.