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Prevalence and breakdown of KRAS driver mutations in a large UK non-small cell lung cancer cohort
  1. Isabella Caroline Chiara Niesner1,2,
  2. Kevin Jon Balbi3,
  3. Benjamin Poskitt3,
  4. Carolina Gemma3,
  5. Josep Linares4,
  6. David Allen4,
  7. Oliver Shutkever5,
  8. Colin R Lindsay6,7,
  9. Philip Bennett3,
  10. David Allan Moore2,5
  1. 1 LMU Klinikum MUM - Muskuloskelettales Universitatszentrum München, München, Germany
  2. 2 Department of Cellular Pathology, University College London Hospitals NHS Foundation Trust, London, UK
  3. 3 Sarah Cannon Molecular Diagnostics, HCA International Ltd, London, UK
  4. 4 HSL Advanded Diagnostics, London, UK
  5. 5 CRUK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK
  6. 6 The University of Manchester Division of Cancer Sciences, Manchester, UK
  7. 7 Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
  1. Correspondence to Dr David Allan Moore; d.moore{at}ucl.ac.uk

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.

  • Diagnostic Techniques and Procedures
  • Lung Neoplasms
  • ONCOGENES

https://doi.org/10.1136/jcp-2024-209972

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    Footnotes

    • Contributors ICCN: data curation, visualisation, formal analysis, writing – original draft, writing – review and editing. KJB: data curation, formal analysis. BP: data curation, formal analysis. CG: data curation, formal analysis. JL: data curation, formal analysis. DA: data curation, formal analysis. OS: visualisation, formal analysis. PB: conceptualisation, writing – review and editing. CRL: conceptualisation, writing – review and editing. DAM (guarantor): conceptualisation, data curation, formal analysis, writing – review and editing.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ICCN, KJB, BP, CG, JL, DA, OS, PB : none. CRL has undertaken advisory work, presented educational material and received research funding from Qiagen. DAM reports speaker fees from AstraZeneca and Takeda, consultancy fees from AstraZeneca, Thermo Fisher, Takeda, Amgen, Janssen and Eli Lilly and has received educational support from Takeda and Amgen.

    • Provenance and peer review Not commissioned; externally peer reviewed.