The Prevalence And Concurrent Pathogenic Mutations Of Kras(G12c) In Northeast Chinese Non-Small-Cell Lung Cancer Patients

Objective: KRAS mutation is one of important driver genes in non-small-cell lung cancer (NSCLC) and the patients with KRAS(G12C) mutations benefit from the inhibitor AMG510. However, the frequency, concurrent pathogenic mutations, and clinical characteristic of KRAS(G12C) is unknown in the NSCLC population of Northeast China.Methods: The retrospective analysis was derived from 431 NSCLC patients in Jilin Cancer Hospital between January 2018 and June 2019. The mutation frequency and concurrent mutations of KRAS(G12C) in tumor or peripheral blood was detected by next-generation sequencing (NGS).Results: The RAS mutant rate was observed in 10.7% (46/431) of this cohort. All RAS-driver cancers are caused by mutations in the KRAS isoform, while the NRAS and HRAS isoforms were not detected. Among KRAS-mutant patients, 42 (91.3%) showed exon 2 mutation in 12 codon and 13 codon. KRAS(G12C) showed a 4.6% (20/431) mutation rate in this cohort and the highest frequency (43.5%, 20/46) in KRAS-mutant-positive patients. There was no difference between tumor tissue and plasma in terms of either KRAS or KRAS(G12C) mutation. The most frequent co-occurrence mutations with KRAS(G12C) were TP53, followed by PTEN. Furthermore, KRAS(G12C) was exclusive with STK11 mutation. KRAS(G12C) mutation was associated with age, disease stage, and smoking status (P=0.024; P=0.02; P=0.006), smoking remained an independent factor for KRAS(G12C) mutation (P=0.037), and higher mutation frequency in patients older than 60, stage I-III, or smoking in NSCLC (P=0.0151, P=0.0343, P=0.0046, respectively).Conclusion: KRAS mutation was the only isoforms of RAS family, of these 43.5% harbored the KRAS(G12C) subtype in northeastern Chinese NSCLC patients. KRAS(G12C) is associated with age, pathological stage and smoking status, more commonly harbored TP53/PTEN mutations, and providing more genome profile for targeted therapy in local clinical practice.