The association between BRAF mutation class and clinical features in BRAF-mutant Chinese non-small cell lung cancer patients

Abstract

BackgroundBRAF mutations occur in 2–4% non-small cell lung cancer (NSCLC) patients and can be categorized into three functional classes based on signaling mechanism and kinase activity: RAS-independent kinase-activating V600 monomers (class 1), RAS-independent kinase-activating dimers (class 2) and RAS-dependent kinase-inactivating heterodimers (class 3). The association between functional classes and clinical features in Chinese NSCLC patients remains unexplored. Our multi-center study aimed to survey the BRAF mutation rate and analyze the associated clinical features in this population.MethodsCapture-based sequencing data of either plasma or tissue samples obtained from 8405 Chinese stage I–IV NSCLC patients were retrospectively analyzed.ResultsBRAF mutations were detected in 238 patients, revealing an overall mutation rate of 2.8%. Among them, 32%, 21% and 13% had BRAF mutant class 1, 2 and 3 respectively. The remaining 34% had other BRAF mutations. V600 (32%) and G469 (13%) were the two most predominant BRAF mutations. Patients with class 2 and 3 mutations were more likely to have concurrent KRAS mutations (P = 0.001). Collectively, BRAF mutations, including non-class 1–3 mutations, were more likely to occur in males (P < 0.01). However, females were more likely to harbor class 1 mutations (P < 0.02). We also compared the overall survival (OS) of first-line chemotherapy-treated advanced-stage patients and revealed comparable OS among the three groups.ConclusionOur study revealed a 2.8% BRAF mutation rate in Chinese NSCLC patients. Our data also showed a male predominance when all BRAF mutations were considered collectively, and a female predominance for class 1 mutations. Furthermore, BRAF V600E is less likely to have concurrent KRAS mutations comparing to the other two classes.