Mutations of the MAPK/TSC/mTOR pathway characterize periventricular glioblastoma with epithelioid SEGA-like morphology-morphological and therapeutic implications.

ABSTRACT: Epithelioid glioblastoma is a recognized glioblastoma variant, recently added to the World Health Organization brain tumor classification, with similar prognosis as the classic variant and B-Raf V600E mutations in 50% of the cases. We identified a new subset of epithelioid glioblastoma with periventricular location and subependymal giant cell astrocytoma (SEGA)-like morphology. Genomic profiling of these tumors revealed driver mutations in NF1, subclonal mutations in TSC1, and a novel driver mutation in MTOR, suggesting upregulation of the MAPK/TSC1/mTOR pathway. Strong mTOR activation was confirmed by immunohistochemistry for the mTOR kinase target 4E-BP1. TSC1 and MTOR mutations have been previously described in low-grade glioma, such as SEGA, and focal

SUBMITTER: Georgescu MM 

PROVIDER: S-EPMC6592288 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature