BRAFnon-V600E more frequently co-occurs with IDH1/2 mutations in adult patients with gliomas than in patients harboring BRAFV600E but without a survival advantage

Abstract

Abstract Background The effects of BRAFnon-V600E and BRAFV600E on the outcomes and the molecular characteristics of adult glioma patients are unknown and need to be explored, although BRAFV600E has been extensively studied in pediatric glioma. Methods Co-occurring mutations and copy number alterations of associated genes in the MAPK and p53 pathways were investigated using data from The Cancer Genome Atlas (TCGA) public database retrieved by cBioPortal. The prognosis of available adult glioma cohorts with BRAFV600E and BRAFnon-V600E mutations were also investigated. Results Ninety patients with BRAFV600E or BRAFnon-V600E were enrolled in this study, and data from 52 nonredundant patients were investigated. Glioblastoma multiform was the most common cancer type, with BRAFnon-V600E and BRAFV600E. TP53 (56.00% vs. 7.41%), IDH1/2 (36.00% vs. 3.70%), and ATRX (32.00% vs. 7.41%) exhibited more mutations in BRAFnon-V600E than in BRAFV600E, and TP53 was an independent risk factor (56.00% vs. 7.41%). Both BRAFnon-V600E and BRAFV600E frequently overlapped with CDKN2A/2B homozygous deletions (HDs), but there was no significant difference. Survival analysis showed no difference between the BRAFnon-V600E and BRAFV600E cohorts, even after excluding the survival benefit of IDH1/2 mutations and considering the BRAFnon-V600E mutations in the glycine-rich loop (G-loop) and in the activation segment. The estimated mean survival of patients with BRAFnon-V600E & IDH1/2WT with mutations in the G-loop groups was the shortest. Conclusions BRAFnon-V600E exhibited a stronger association with IDH1/2 mutations than BRAFV600E, but no survival advantage was found.