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

Background: The effects of BRAF^non-V600E and BRAF^V600E on the outcomes and the molecular characteristics of adult glioma patients are unknown and need to be explored, although BRAF^V600E 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 BRAF^V600E and BRAF^non-V600E mutations were also investigated.

Results: Ninety patients with BRAF^V600E or BRAF^non-V600E were enrolled in this study, and data from 52 nonredundant patients were investigated. Glioblastoma multiform was the most common cancer type, with BRAF ^non-V600E and BRAF^V600E. TP53 (56.00% vs. 7.41%), IDH1/2 (36.00% vs. 3.70%), and ATRX (32.00% vs. 7.41%) exhibited more mutations in BRAF^non-V600E than in BRAF^V600E, and TP53 was an independent risk factor (56.00% vs. 7.41%). Both BRAF^non-V600E and BRAF^V600E frequently overlapped with CDKN2A/2B homozygous deletions (HDs), but there was no significant difference. Survival analysis showed no difference between the BRAF ^non-V600E and BRAF^V600E cohorts, even after excluding the survival benefit of IDH1/2 mutations and considering the BRAF^non-V600E mutations in the glycine-rich loop (G-loop) and in the activation segment. The estimated mean survival of patients with BRAF^non-V600E & IDH1/2^WT with mutations in the G-loop groups was the shortest.

Conclusions: BRAF^non-V600E exhibited a stronger association with IDH1/2 mutations than BRAF^V600E, but no survival advantage was found.

Keywords: Adult patient with glioma; BRAF V600E; BRAF non-V600E; IDH1/2.