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

Yan Liu; Hui Li; Jing Zhu; Yang Zhang; Xianhong Liu; Rixin Li; Qiang Zhang; Ying Cheng

doi:10.2147/CMAR.S282617

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

Cancer Manag Res. 2021 Mar 15:13:2447-2454. doi: 10.2147/CMAR.S282617. eCollection 2021.

Authors

Yan Liu¹, Hui Li¹, Jing Zhu², Yang Zhang², Xianhong Liu², Rixin Li¹, Qiang Zhang³, Ying Cheng^{1

2}

Affiliations

¹ Medical Oncology Translational Research Lab, Jilin Provincial Key Laboratory of Molecular Diagnostics for Lung Cancer, Jilin Cancer Hospital, Changchun, 130012, People's Republic of China.
² Department of Medical Thoracic Oncology, Jilin Cancer Hospital, Changchun, 130012, People's Republic of China.
³ Department of Bioinformatics, Burning Rock Biotech, Guangzhou, People's Republic of China.

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: KRASG12C; mutations; next-generation sequencing; non-small-cell lung cancer; plasma; tissue.