Open AccessBRAF V600E mutant oligodendroglioma‐like tumors with chromosomal instability in adolescents and young adults
Author(s) -
Fukuoka Kohei,
Mamatjan Yasin,
Ryall Scott,
Komosa Martin,
Bennett Julie,
Zapotocky Michal,
Keith Julia,
Myrehaug Sten,
Hazrati LiliNaz,
Aldape Kenneth,
Laperriere Norm,
Bouffet Eric,
Tabori Uri,
Hawkins Cynthia
Publication year - 2020
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12799
Subject(s) - oligodendroglioma , idh1 , chromosome instability , glioma , biology , pathology , pathological , cancer research , histology , mutation , chromosome , medicine , astrocytoma , genetics , gene
We performed genome‐wide methylation analysis on 136 pediatric low‐grade gliomas, identifying a unique cluster consisting of three tumors with oligodendroglioma‐like histology, BRAF p.V600E mutations and recurrent whole chromosome gains of 7 and loss of 10. Morphologically, all showed similar features, including a diffusely infiltrative glioma composed of round nuclei with perinuclear halos, a chicken‐wire pattern of branching capillaries and microcalcification. None showed astrocytic features or characteristics suggestive of high‐grade tumors including necrosis or mitotic figures. All tumors harbored multiple chromosomal copy number abnormalities (>10 chromosomes altered), but none showed 1p/19q co‐deletion or IDH1 p.R132H mutation. Hierarchical clustering and t‐stochastic neighbor embedding analyses from DNA methylation data cluster them more closely to previously described pediatric‐type low‐grade gliomas and separate from adult gliomas. These tumors exhibit distinct clinical features; they are temporal lobe lesions occurring in adolescents and young adults with a prolonged history of seizures and all are alive with no recurrence (follow‐up 3.2 to 13.2 years). We encountered another young adult case with quite similar pathological appearance and molecular status except for TERT promoter mutation. Although the series is small, these may represent a new category of IDH wild‐type low‐grade gliomas which may be confused with “molecular GBM.” Further, they highlight the heterogeneity of IDH wild‐type gliomas and the relatively indolent behavior of “pediatric‐type” gliomas.