Prevalence and breakdown of KRAS driver mutations in a large UK non-small cell lung cancer cohort
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Updated: May 29, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Isabella Caroline Chiara Niesner1,2, Kevin Jon Balbi3, Benjamin Poskitt3
1LMU Klinikum MUM - Muskuloskelettales Universitatszentrum München, München, Germany.
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.
Insights
KRAS mutations are common in UK lung cancer patients, with G12C, G12V, and G12D being most prevalent. Co-occurring PIK3CA and BRAF mutations were frequent, and PD-L1 expression did not differ between KRAS wild-type and mutant tumors.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Kirsten rat sarcoma viral oncogene (KRAS) is a key oncogene in lung cancer development.
- KRAS mutations, particularly G12C, are targets for novel therapies.
- Geographical variations exist in non-small cell lung cancer (NSCLC) driver mutations.
Purpose of the Study:
- To analyze the KRAS mutation spectrum in a large UK cohort of NSCLC patients.
- To investigate co-occurring oncogenic mutations and their frequencies.
- To assess the association between KRAS mutation status and PD-L1 expression.
Main Methods:
- Interrogation of archival clinical next-generation sequencing (NGS) data from 3283 NSCLC samples over 5 years.
- Analysis of somatic mutation hotspots in cancer-associated genes using ampliseq/ion-torrent based NGS assays.
- Collated PD-L1 scores from a subset of the cohort.
Main Results:
- A total of 1118 KRAS variants were detected, with Class I mutations being the most frequent (86.94%).
- KRAS G12C, G12V, and G12D were the most prevalent mutations.
- PIK3CA and BRAF mutations were the most common co-mutations; no significant difference in PD-L1 expression was observed between KRAS wild-type and mutant tumors.
Conclusions:
- This study provides a comprehensive overview of KRAS mutations and co-mutations in a UK NSCLC population.
- The findings highlight the prevalence of specific KRAS variants and common co-occurring mutations.
- PD-L1 expression is not significantly influenced by KRAS mutation status in this cohort.
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