Somatic Cancer Genetics in the UK: Real-World Data from Phase One of the Cancer Research UK Stratified Medicine Programme

Colin R Lindsay, Emily Shaw, Fiona Blackhall, Kevin G Blyth, James D Brenton, Anshuman Chaturvedi, Noel W Clarke, Craig Dick, Thomas RJ Evans, Geoff Hall, Andrew M. Hanby, David Harrison, Stephen Johnston, Malcolm D Mason, Dion Morton, Julia Newton-Bishop, Andrew G. Nicholson, Karen A Oien, Sanjay Popat, Doris M RasslRowena Sharpe, Phillipe Taniere, Ian Walker, William Wallace, Nicholas P West, Rachel Butler, David Gonzales de Castro, Mike Griffiths, Peter WM Johnson

Research output: Contribution to journalArticlepeer-review

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, recruiting samples from 7,814 patients for genetic examination between 2011-2013. Tumor types involved were breast, colorectal, lung, prostate, ovary 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 National Cancer Research Institute Clinical Study groups.
Results
10,754 patients (98% of those approached) consented to participate, from which 7,814 tumor samples were genetically analysed. In total, 53% had at least one genetic aberration detected. From 1885 lung cancer patients, 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-tumor 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 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.
Original languageEnglish
JournalESMO Open
Early online date5 Sep 2018
DOIs
Publication statusE-pub ahead of print - 5 Sep 2018

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