The Prevalence and Concurrent Pathogenic Mutations of KRAS^G12C in Northeast Chinese Non-small-cell Lung Cancer Patients

Abstract

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.

Keywords:

• next-generation sequencing
• non-small-cell lung cancer
• KRAS^G12C
• tissue
• plasma
• mutations

Acknowledgments

This research was supported by Scientific Research Project of Jilin Provincial Health and Family Planning Commission (grant numbers 2018Q007, 2019J077); Science and Technology Agency of Jilin Provincial Project (grant numbers 20200201518JC, 202002063JC); Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China (grant numbers 2020ZX09201-024).

Disclosure

Qiang Zhang is an employee of Burning Rock Biotech. The authors report no other potential conflicts of interests in this work.