Cancer Management and Research (Mar 2021)
The Prevalence and Concurrent Pathogenic Mutations of KRASG12C in Northeast Chinese Non-small-cell Lung Cancer Patients
Abstract
Yan Liu,1 Hui Li,1 Jing Zhu,2 Yang Zhang,2 Xianhong Liu,2 Rixin Li,1 Qiang Zhang,3 Ying Cheng1,2 1Medical Oncology Translational Research Lab, Jilin Provincial Key Laboratory of Molecular Diagnostics for Lung Cancer, Jilin Cancer Hospital, Changchun, 130012, People’s Republic of China; 2Department of Medical Thoracic Oncology, Jilin Cancer Hospital, Changchun, 130012, People’s Republic of China; 3Department of Bioinformatics, Burning Rock Biotech, Guangzhou, People’s Republic of ChinaCorrespondence: Ying ChengJilin Cancer Hospital, No. 1066 Jinhu Road, Chaoyang District, Changchun, Jilin Province, 130012, People’s Republic of ChinaTel +86 43185879901Email [email protected]: KRAS mutation is one of important driver genes in non-small-cell lung cancer (NSCLC) and the patients with KRASG12C mutations benefit from the inhibitor AMG510. However, the frequency, concurrent pathogenic mutations, and clinical characteristic of KRASG12C 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 KRASG12C 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. KRASG12C 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 KRASG12C mutation. The most frequent co-occurrence mutations with KRASG12C were TP53, followed by PTEN. Furthermore, KRASG12C was exclusive with STK11 mutation. KRASG12C 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 KRASG12C 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 KRASG12C subtype in northeastern Chinese NSCLC patients. KRASG12C 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.Keywords: next-generation sequencing, non-small-cell lung cancer, KRASG12C, tissue, plasma, mutations
