BRAF V600E mutant oligodendroglioma-like tumors with chromosomal instability in adolescents and young adults

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.