Introduction:
The coal-manufacturing districts in the Eastern Yunnan province of Southwest China have the highest rates of occurrence and death from lung tumors. Unique clinical characteristics of non-small cell lung cancer (NSCLC) in patients from these regions were previously reported without a clear understanding of the etiology and molecular characteristics. We aim to identify the unique driver gene mutation spectrum.

Material and methods:
Samples from 1120 NSCLC patients from Eastern Yunnan were gathered for next-generation sequencing. Seventeen gene targets were sequenced. We compared individuals’ medical and genetic features from the coal- and non-coal-manufacturing zones.

Results:
The 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 regions. EGFR with KRAS, BRAF, RET, and TP53 with ALK and KRAS were mutually exclusive. Mutations in the TP53 signaling pathways were the most common in NSCLC patients from the coal-producing districts.

Conclusions:
Our 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.