Send to

Choose Destination
Brain Pathol. 2019 Oct 19. doi: 10.1111/bpa.12799. [Epub ahead of print]

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

Author information

Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
Princess Margaret Cancer Centre and MacFeeters, Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Program in Genetics and Genome Biology, The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Radiation Oncology, Princess Margaret Hospital, Toronto, ON, Canada.


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.


BRAF V600E mutation; chromosomal instability; low grade glioma; oligodendroglioma


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center