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- Title
The genetic landscape of ganglioglioma.
- Authors
Pekmezci, Melike; Villanueva-Meyer, Javier E.; Goode, Benjamin; Van Ziffle, Jessica; Onodera, Courtney; Grenert, James P.; Bastian, Boris C.; Chamyan, Gabriel; Maher, Ossama M.; Khatib, Ziad; Kleinschmidt-DeMasters, Bette K.; Samuel, David; Mueller, Sabine; Banerjee, Anuradha; Clarke, Jennifer L.; Cooney, Tabitha; Torkildson, Joseph; Gupta, Nalin; Theodosopoulos, Philip; Chang, Edward F.
- Abstract
Ganglioglioma is the most common epilepsy-associated neoplasm that accounts for approximately 2% of all primary brain tumors. While a subset of gangliogliomas are known to harbor the activating p.V600E mutation in the <italic>BRAF</italic> oncogene, the genetic alterations responsible for the remainder are largely unknown, as is the spectrum of any additional cooperating gene mutations or copy number alterations. We performed targeted next-generation sequencing that provides comprehensive assessment of mutations, gene fusions, and copy number alterations on a cohort of 40 gangliogliomas. Thirty-six harbored mutations predicted to activate the MAP kinase signaling pathway, including 18 with <italic>BRAF</italic> p.V600E mutation, 5 with variant <italic>BRAF</italic> mutation (including 4 cases with novel in-frame insertions at p.R506 in the β3-αC loop of the kinase domain), 4 with <italic>BRAF</italic> fusion, 2 with <italic>KRAS</italic> mutation, 1 with <italic>RAF1</italic> fusion, 1 with biallelic <italic>NF1</italic> mutation, and 5 with <italic>FGFR1/2</italic> alterations. Three gangliogliomas with <italic>BRAF</italic> p.V600E mutation had concurrent <italic>CDKN2A</italic> homozygous deletion and one additionally harbored a subclonal mutation in <italic>PTEN</italic>. Otherwise, no additional pathogenic mutations, fusions, amplifications, or deletions were identified in any of the other tumors. Amongst the 4 gangliogliomas without canonical MAP kinase pathway alterations identified, one epilepsy-associated tumor in the temporal lobe of a young child was found to harbor a novel <italic>ABL2</italic>-<italic>GAB2</italic> gene fusion. The underlying genetic alterations did not show significant association with patient age or disease progression/recurrence in this cohort. Together, this study highlights that ganglioglioma is characterized by genetic alterations that activate the MAP kinase pathway, with only a small subset of cases that harbor additional pathogenic alterations such as <italic>CDKN2A</italic> deletion.
- Subjects
GENETICS of epilepsy; BRAIN tumor genetics; ONCOGENES
- Publication
Acta Neuropathologica Communications, 2018, Vol 6, Issue 1, pN.PAG
- ISSN
2051-5960
- Publication type
Article
- DOI
10.1186/s40478-018-0551-z