Diffuse leptomeningeal glioneuronal tumour

From Compendium of Cancer Genome Aberrations
Revision as of 13:45, 21 April 2026 by Richard.Glen (talk | contribs) (Added Missing Sections)

(diff) ← Older revision | Approved revision (diff) | Latest revision (diff) | Newer revision → (diff)
Jump to navigation Jump to search


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].

Additional Information

Put your text here

Links

Put a link here or anywhere appropriate in this page (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 "http://www." portion.)

References

  1. ↑ Valiakhmetova, Andge; Papusha, Ludmila; Yasko, Ludmila; Druy, Alexander; Karachunsky, Alexander; Novichkova, Galina; Hwang, Eugene I; Packer, Roger J (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.
  2. ↑ Deng, Maximilian Y.; Sill, Martin; Chiang, Jason; Schittenhelm, Jens; Ebinger, Martin; Schuhmann, Martin U.; Monoranu, Camelia-Maria; Milde, Till; Wittmann, Andrea (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. {{cite journal}}: Check date values in: |date= (help)
  3. ↑ Deng, Maximilian Y.; Sill, Martin; Chiang, Jason; Schittenhelm, Jens; Ebinger, Martin; Schuhmann, Martin U.; Monoranu, Camelia-Maria; Milde, Till; Wittmann, Andrea (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. {{cite journal}}: Check date values in: |date= (help)
  4. ↑ Deng, Maximilian Y.; Sill, Martin; Chiang, Jason; Schittenhelm, Jens; Ebinger, Martin; Schuhmann, Martin U.; Monoranu, Camelia-Maria; Milde, Till; Wittmann, Andrea (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. {{cite journal}}: Check date values in: |date= (help)
  5. ↑ Deng, Maximilian Y.; Sill, Martin; Chiang, Jason; Schittenhelm, Jens; Ebinger, Martin; Schuhmann, Martin U.; Monoranu, Camelia-Maria; Milde, Till; Wittmann, Andrea (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. {{cite journal}}: Check date values in: |date= (help)
  6. ↑ Chiang, Jason; Dalton, James; Upadhyaya, Santhosh A.; Patay, Zoltán; Qaddoumi, Ibrahim; Li, Xiaoyu; Segura, Annette D.; Sharma, Suash; Ismail, Azzam (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. {{cite journal}}: Check date values in: |date= (help)
  7. ↑ Deng, Maximilian Y.; Sill, Martin; Chiang, Jason; Schittenhelm, Jens; Ebinger, Martin; Schuhmann, Martin U.; Monoranu, Camelia-Maria; Milde, Till; Wittmann, Andrea (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. {{cite journal}}: Check date values in: |date= (help)
  8. ↑ Rodriguez, Fausto J.; Schniederjan, Matthew J.; Nicolaides, Theo; Tihan, Tarik; Burger, Peter C.; Perry, Arie (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. {{cite journal}}: Check date values in: |date= (help)
  9. ↑ Deng, Maximilian Y.; Sill, Martin; Chiang, Jason; Schittenhelm, Jens; Ebinger, Martin; Schuhmann, Martin U.; Monoranu, Camelia-Maria; Milde, Till; Wittmann, Andrea (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. {{cite journal}}: Check date values in: |date= (help)
  10. ↑ Dodgshun, Andrew J.; SantaCruz, Nadine; Hwang, Jaeho; Ramkissoon, Shakti H.; Malkin, Hayley; Bergthold, Guillaume; Manley, Peter; Chi, Susan; MacGregor, Duncan (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. {{cite journal}}: Check date values in: |date= (help)
  11. ↑ Appay, Romain; Pages, Mélanie; Colin, Carole; Jones, David T. W.; Varlet, Pascale; Figarella-Branger, Dominique (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. PMID 32605662.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  12. ↑ Valiakhmetova, Andge; Papusha, Ludmila; Yasko, Ludmila; Druy, Alexander; Karachunsky, Alexander; Novichkova, Galina; Hwang, Eugene I; Packer, Roger J (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.
  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.
  14. ↑ Appay, Romain; Pages, Mélanie; Colin, Carole; Jones, David T. W.; Varlet, Pascale; Figarella-Branger, Dominique (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. PMID 32605662.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  15. ↑ Deng, Maximilian Y.; Sill, Martin; Chiang, Jason; Schittenhelm, Jens; Ebinger, Martin; Schuhmann, Martin U.; Monoranu, Camelia-Maria; Milde, Till; Wittmann, Andrea (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. {{cite journal}}: Check date values in: |date= (help)
  16. ↑ Deng, Maximilian Y.; Sill, Martin; Chiang, Jason; Schittenhelm, Jens; Ebinger, Martin; Schuhmann, Martin U.; Monoranu, Camelia-Maria; Milde, Till; Wittmann, Andrea (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. {{cite journal}}: Check date values in: |date= (help)
  17. ↑ Dodgshun, Andrew J.; SantaCruz, Nadine; Hwang, Jaeho; Ramkissoon, Shakti H.; Malkin, Hayley; Bergthold, Guillaume; Manley, Peter; Chi, Susan; MacGregor, Duncan (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. {{cite journal}}: Check date values in: |date= (help)

Notes

*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 Associate Editor 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.

Retrieved from "https://content.ccga.io/index.php?title=CNS5:Diffuse_leptomeningeal_glioneuronal_tumour&oldid=21116"