Somatic cancer genetics in the UK: real-world data from phase I of the Cancer Research UK Stratified Medicine Programme

Lindsay, C. R. et al. (2018) Somatic cancer genetics in the UK: real-world data from phase I of the Cancer Research UK Stratified Medicine Programme. ESMO Open, 3(6), e000408. (doi: 10.1136/esmoopen-2018-000408) (PMID:30233821) (PMCID:PMC6135448)

Abstract

Introduction: Phase I of the Cancer Research UK Stratified Medicine Programme (SMP1) was designed to roll out molecular pathology testing nationwide at the point of cancer diagnosis, as well as facilitate an infrastructure where surplus cancer tissue could be used for research. It offered a non-trial setting to examine common UK cancer genetics in a real-world context. Methods: A total of 26 sites in England, Wales and Scotland, recruited samples from 7814 patients for genetic examination between 2011 and 2013. Tumour types involved were breast, colorectal, lung, prostate, ovarian cancer and malignant melanoma. Centralised molecular testing of surplus material from resections or biopsies of primary/metastatic tissue was performed, with samples examined for 3–5 genetic alterations deemed to be of key interest in site-specific cancers by the National Cancer Research Institute Clinical Study groups. Results: 10 754 patients (98% of those approached) consented to participate, from which 7814 tumour samples were genetically analysed. In total, 53% had at least one genetic aberration detected. From 1885 patients with lung cancer, KRAS mutation was noted to be highly prevalent in adenocarcinoma (37%). In breast cancer (1873 patients), there was a striking contrast in TP53 mutation incidence between patients with ductal cancer (27.3%) and lobular cancer (3.4%). Vast inter-tumour heterogeneity of colorectal cancer (1550 patients) was observed, including myriad double and triple combinations of genetic aberrations. Significant losses of important clinical information included smoking status in lung cancer and loss of distinction between low-grade and high-grade serous ovarian cancers. Conclusion: Nationwide molecular pathology testing in a non-trial setting is feasible. The experience with SMP1 has been used to inform ongoing CRUK flagship programmes such as the CRUK National Lung MATRIX trial and TRACERx.

• Item Type: Articles
• Additional Information: Funding for the Stratified Medicine Programme is acknowledged from Cancer Research UK and programme founding partners AstraZeneca and Pfizer. For hosting the Stratified Medicine Programme data, thanks to the National Cancer Registration Service Eastern Office, Jim Davies and Steve Harris at the University of Oxford Department of Computer Science. AGN was supported by the National Institute of Health Research Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. PJ, ES and CL have all been employed by Cancer Research UK in the past. FB was supported by Cancer Research UK Lung Cancer Centre of Excellence Funding. WAW was supported by Lothian NRS BioResource. SP acknowledges NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the ICR. NPW is supported by Yorkshire Cancer Research. KGB is supported by a NHS Research Scotland Senior Fellowship.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kean, Ms Sharon and Dick, Dr Craig and Grant, David and Blyth, Professor Kevin and Oien, Professor Karin and Flood, Ms Marion and Ford, Professor Ian and Evans, Professor Jeff
• Authors: Lindsay, C. R., Shaw, E. C., Blackhall, F., Blyth, K. G., Brenton, J. D., Chaturvedi, A., Clarke, N., Dick, C., Evans, T. R.J., Hall, G., Hanby, A. M., Harrison, D. J., Johnston, S., Mason, M. D., Morton, D., Newton-Bishop, J., Nicholson, A. G., Oien, K. A., Popat, S., Rassl, D., Sharpe, R., Taniere, P., Walker, I., Wallace, W. A., West, N. P., Butler, R., Gonzales de Castro, D., Griffiths, M., Johnson, P. W.M., Ford, I., Kean, S., Flood, M., and Grant, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: ESMO Open
• Publisher: BMJ Publishing Group
• ISSN: 2059-7029
• ISSN (Online): 2059-7029
• Published Online: 05 September 2018
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in ESMO Open 3(6): e000408
• Publisher Policy: Reproduced under a Creative Commons License