Prevalence and breakdown of KRAS driver mutations in a large UK non-small cell lung cancer cohort
Niesner, I. C. C. Balbi, K. J. Poskitt, B. Gemma, C. Linares, J. Allen, D. Shutkever, O. Lindsay, C. R. Bennett, P. Moore, D. A.
Niesner, I. C. C.
Balbi, K. J.
Poskitt, B.
Gemma, C.
Linares, J.
Allen, D.
Shutkever, O.
Lindsay, C. R.
Bennett, P.
Moore, D. A.
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.
Description
Date
2025
Publisher
Collections
Keywords
Type
Article
Citation
Niesner ICC, Balbi KJ, Poskitt B, Gemma C, Linares J, Allen D, et al. Prevalence and breakdown of KRAS driver mutations in a large UK non-small cell lung cancer cohort. Journal of clinical pathology. 2025 Apr 17;78(5):346-50. PubMed PMID: 39890446. Epub 2025/02/01 20:44. eng.