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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

1
Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
2
Princess Margaret Cancer Centre and MacFeeters, Hamilton Centre for Neuro-Oncology Research, Toronto, ON, Canada.
3
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
4
Program in Genetics and Genome Biology, The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
5
Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
6
Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
7
Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
8
Department of Radiation Oncology, Princess Margaret Hospital, Toronto, ON, Canada.

Abstract

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.

KEYWORDS:

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

PMID:
31630459
DOI:
10.1111/bpa.12799

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