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-RafV600E mutations in 50% of the cases.
Because mutations of FANCA and BRAF and copy number variations of CDKN2A/B are more frequent in PXA than in glioblastoma, they might be used to distinguish the 2 tumors.
Here, we describe a case of systemic metastases of a clonal subpopulation of BRAFV600E mutated glioblastoma in a patient previously treated with surgery, radiation, temozolomide and bevacizumab.
Besides, more benign brain tumors such as ganglioglioma, dysembryoblastic neuroepithelial tumours and supratentorial pilocytic astrocytomas, only pleomorphic xanthoastrocytomas (50-78%) and epitheloid glioblastoma (50%) regularly exhibit BRAF mutations.
The regulation of TORC1 signaling by BRAF was examined in BT-40 (BRAF mutant) and BT-35 (BRAF wild type) xenografts, in a cell line derived from the BT-40 xenograft and two adult BRAF mutant glioblastoma cell lines.
An institutional cohort of 105 brain tumors (51 dysembryoplastic neuroepithelial tumors (DNTs), 14 subependymal giant cell astrocytomas (SEGAs), 12 glioblastoma with neuronal marker expression (GBM-N), and 28 pleomorphic xanthoastrocytomas (PXAs)) from 100 patients were investigated for the presence of BRAF(V600E) by direct sequencing.
In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations.
In our analysis we detect BRAFV600E mutations in 12 of 20 (60%) WHO grade II PXA, in 1 of 6 (17%) PXA with anaplasia and in 1 glioblastoma arising in a PXA.