BRAF-amplified glioblastoma patients have a worse prognosis than those with BRAF mutation and are associated with amplification of MET, RHEB and CUL1

BACKGROUND: Glioblastoma (GBM) is a treatment-challenging disease with a poor prognosis and few treatment options available. Patients with GBM with BRAF gene mutations are expected to benefit from targeted therapy with BRAF inhibitors. METHODS: Genomic profiles, clinical and sample data, and tumor pathways were retrieved in a cohort of GBM patients with BRAF gene alterations. Statistical analysis was performed according to BRAF AMP, BRAF V600E, and BRAF non-V600E to study clinical features, survival curve analysis, tumor site, tumor signaling pathway and molecules. RESULTS: BRAF AMP and BRAF MUT include BRAF V600E and BRAF non-V600E in GBM patients account for the majority of BRAF-altered GBM. The prognosis of GBM patients with BRAF AMP is worse than that of patients with BRAF MUT, as well as BRAF V600E and BRAF non-V600E. The temporal lobe was primarily affected in GBM patients who carry BRAF gene alterations. CDKN2A DeepDel is a mutation associated with the BRAF variant GBM. In addition, BRAF AMP is often accompanied by amplified oncogenes, including MET, RHEB, and CUL1, as well as multiple types of mutations result in tumor suppressor genes in patients with BRAF non-V600E GBM including NF1 and TP53. CONCLUSIONS: Different BRAF gene alterations affect the prognosis of GBM and are associated with molecular alterations in classical tumor signaling pathways, and BRAF AMP is often accompanied by amplification of MET, RHEB, and CUL1.