Prevalence and breakdown of KRAS driver mutations in a large UK non-small cell lung cancer cohort.

Abstract

Kirsten rat sarcoma viral oncogene (KRAS) is a frequently mutated oncogene in lung cancer, now amenable to targeted therapy with allele-specific G12C inhibitors. Non-small cell lung cancer (NSCLC) driver mutations show geographical variability and therefore the KRAS mutation breakdown, co-occurring oncogenic mutation rate and associated PD-L1 expression were studied in a large UK cohort. We interrogated archival clinical next-generation sequencing (NGS) data over 5 years. 3283 NSCLC samples were included, referred from 38 centres over 4 years. Somatic mutation hotspots in cancer-associated genes were analysed using ampliseq/ion-torrent based NGS assays. In a subset of the cohort, PD-L1 scores were also collated. 1118 KRAS variants were detected. Class I mutations occurred most frequently (86.94%), with KRAS G12C, G12V and G12D being most prevalent. Class II (7.96%), III (4.65%) and IV (0.45%) mutations were also detected and mutations in PIK3CA and BRAF were the most frequently observed co-mutations. No significant difference in PD-L1 expression was found between KRAS wild-type and mutant tumours.