Unique Spectrum of Driver Gene Mutations in Patients with Non-Small Cell Lung Carcinoma (NSCLC) from Coal-manufacturing Districts in Southwest China

Abstract

IntroductionThe coal-manufacturing districts in the Eastern Yunnan province of Southwest China are the utmost occurrence and death of lung tumors. As previously reported on unique clinical characteristics of non-small cell lung cancer (NSCLC) in patients from these regions without a clear understanding of the aetiology and molecular characteristics. We aim to identify the unique driver gene mutations spectrum.Material and methodsSamples from 1120 NSCLC patients from Eastern Yunnan were gathered for next-generation sequencing. Seventeen gene targets were sequenced. We have compared individuals' medical and genetic features from the coal- and non-coal-manufacturing zones.ResultsThe mutation rates of EGFR (L858R, 19-Del, G719X+L861X, L858R+EGFR amplification) and ERBB2 (20ins) were low in patients from coal-manufacturing regions. Interestingly, EGFR (G719X, S768I, G719X+S768I), KRAS (G12C), TP53 (R158L) and NTRK3 demonstrated a much higher mutation frequency. Furthermore, EGFR compound mutations were linked with the patient's job and TNM staging IIIb-IV. The OncodriverCLUST algorithm authenticated 6 genes (KRAS, EGFR, ROS1, NRAS, BRAF, and ERBB2) as driver genes in patients from coal manufacturing. EGFR with KRAS, BRAF, RET, and TP53 with ALK and KRAS were mutually exclusive. Mutations in the TP53 signaling pathway were the most common in NSCLC patients from the coal-fabricating districts.ConclusionsOur analyses confirmed the unique spectrum of driver genetic mutations and emphasized the potential of future targeted therapy in NSCLC patients from the coal-manufacturing districts of Eastern Yunnan. Our data broaden the view of NSCLC pathogenesis and its relationship with the environmental conditions in coal-producing regions.