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.
Epithelioid GBM with BRAFV600E mutation can be considered a good treatment indication for precision medicine, and this patient-derived cell line should be useful for prediction of the tumor response and clarification of its biological characteristics.
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.
Vemurafenib is a targeted therapy that has mainly been used for the treatment of melanoma patients for several years, and as a possible alternative treatment for cases of GBM harboring BRAF mutations, its existence may make testing for BRAF status important.
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.
These results illustrate the need for a new therapeutic approach, such as molecular targeted drug therapy like BRAF inhibition, in addition to standard chemoradiotherapy for typical GBM.
Our data suggest routine screening for BRAFV600E mutations for glioblastomas WHO grade IV below the age of 30, especially in glioblastomas with epithelioid features and in all rhabdoid meningiomas WHO grade III.
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.
We report here the detection of the BRAFV600E mutation in a patient with c-GBM and describe the patient's clinical course as well as the results of histopathological analysis.
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.
We tested our originally reported cohort of 8 E-GBMs and 2 rhabdoid GBMs (R-GBM) as well as 5 new E-GBMs (1 pediatric, 4 adult) and 9 GC-GBMs (2 pediatric, 7 adult) (n=24) for BRAFV600E mutational status.