P3.03-01 BRAF V600 and Non-V600 Mutations in Chinese Lung Cancer

Abstract

BRAF gene mutation, especially V600E, was frequently mutated in cancer. Vemurafenib and dabrafenib has already been approved in melanoma as well as NSCLC and preclinical studies have demonstrated promising results in non-V600 NSCLC. But the landscape of BRAF non-V600 mutation in Chinsese lung cancer was rarely descripted. 7,417 normal-paired samples from lung cancer patients were analyzed using hybridization capture-based next generation sequencing and alterations including single nucleotide variants (SNVs), short insertions/deletions (indels), copy number variations (CNVs) and structural variations (SV) were analyzed. BRAF was altered in 1.8% (133 of 7,417) of all tumors. BRAF V600 (gain of function, GOF) and non-V600 mutations (GOF: G469V/R/E/A, K601N/E, L597V/R, T599dup/T599R, N486_P490del, L525R, and loss of function/LOF: D594N/G, N581S/I, G466V/A, K483E, G596R), has previously been reported to increase MEK/ERK activation, were detected in 52.3% (58/111) and 47.7% (53/111) of BRAF functional mutation patients. CNVs and SVs were both observed at a frequency of 0.9% (1/111). Two patients have two GOF mutations (V600E/T599R). We also found that 82.0% (91/111) of the BRAF functional mutation carriers also owned the other actionable or driver mutation, the most frequent one was TP53 (68.1%), then was EGFR (18.7%), KRAS/NRAS (14.3%), PIK3CA (11.0%) as well as CDKN2A/B (9.9%). BRAF gene mutations, non-V600 especially, was extensively mutated in Chinese lung cancer. This work supports a broad profiling approach in lung cancers and suggests that non-V600E BRAF alterations represent a subgroup of lung cancers in which targeted therapy should be considered.