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.
Recent studies have shown the existence of BRAF alterations in ganglioglioma (GG), pilocytic astrocytoma (PA), pleomorphic xanthoastrocytomas (PXA), and epithelioid glioblastoma (eGBM).
Univariate analysis demonstrated that abundant epithelioid cells, extensive necrosis, EZH2 overexpression and BRAFV600E mutations were significantly associated with decreased overall survival in EGBM and APXA patients (P < 0.05).
Neuropathology revealed a highly aggressive molecular subtype of the epithelioid glioblastoma without an isocitrate dehydrogenase and B-Raf proto-oncogene mutation or a O6-methylguanine-DNA-methyltransferase promoter hypermethylation.
Dramatic response of BRAFV600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor: establishment and xenograft of a cell line to predict clinical efficacy.
Molecular results demonstrated that the prevalence of BRAFV600E, TERT promoter mutations and CDKN2A/B homozygous deletions in E-GBM were 13/14 (93%), 10/14 (71%) and 11/14 (79%), respectively, and concurrent BRAFV600E, TERT promoter mutations and CDKN2A/B homozygous deletions were observed in 7/14 (50%) of E-GBM.
Histopathological examination confirmed an isocitrate dehydrogenase-wild-type epithelioid glioblastoma with a BRAFV600E mutation, but the original slow-growing lesion was no longer detected.
Demonstration of concurrent BRAFV600E and TERT promoter mutations in low- and high-grade lesions strongly suggested their identical origin, and acquisition of each mutation may be an early event, possibly playing a pivotal role in the genesis and subsequent progression to E-GBM.
To the best of our knowledge, this is the first report demonstrating a discrepancy in the BRAFV600E mutation states between epithelioid glioblastoma and colocalized low-grade astrocytoma.
A valine-to-glutamic acid substitution at position 600 of the serine/threonine-protein kinase BRAF (BRAFV600E) mutation, which is commonly found in PXA, has recently been detected in approximately 50% of all epithelioid glioblastoma (GBM) cases.
BRAF mutation at T1799 > A (V600E) was detected in 4/12 (33.3%) PXA and 4/8 (50.0%) eGBM, while TERT-p mutation was detected at C228 > T in 2/12 (16.7%) PXA and at C250 > T in 1/8 (12.5%) eGBM.
Immunohistochemical and molecular biological assessment for isocitrate dehydrogenases 1 and 2 (IDH1/2), α-thalassemia/mental-retardation-syndrome-X-linked gene (ATRX), p53, BRAF, telomere reverse transcriptase promoter (TERT-p), H3F3A, and integrase interactor 1 (INI1) were performed. eGBM tended to lack the degenerative changes characteristic for PXA.
In conclusion, E-GBM frequently exhibit BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions and these alterations tend to coexist in E-GBM.
In conclusion, E-GBM frequently exhibit BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions and these alterations tend to coexist in E-GBM.
A number of studies have demonstrated that more than half of E-GBMs harbor a valine to glutamic acid substitution at position 600 of the serine/threonine-protein kinase BRAF (BRAF V600E).
A number of studies have demonstrated that more than half of E-GBMs harbor a valine to glutamic acid substitution at position 600 of the serine/threonine-protein kinase BRAF (BRAF V600E).
We identified a subset of tumors (n = 18, 8.8% of high-grade gliomas) exhibiting moderate-to-strong immunoreactivity that enriched for the IDH-wild-type glioblastoma variants gliosarcoma (n = 10) and the newly described epithelioid glioblastoma (n = 4).
A number of studies have demonstrated that more than half of E-GBMs harbor a valine to glutamic acid substitution at position 600 of the serine/threonine-protein kinase BRAF (BRAF V600E).
A number of studies have demonstrated that more than half of E-GBMs harbor a valine to glutamic acid substitution at position 600 of the serine/threonine-protein kinase BRAF (BRAF V600E).