Opportunities for precision oncology revealed by whole genome sequencing 10,478 cancers - the UK 100,000 Genomes Project

Identifying cancer driver genes is key for delivering the vision of precision oncology. The falling cost makes whole genome sequencing (WGS) attractive as a single all-encompassing test to identify uncommon cancer drivers in a patient, which may not be captured by panel testing but are potentially targeted by small molecules. We analysed 10,478 patient tumour genomes spanning 35 cancer types recruited to the UK 100,000 Genomes Project. We identified 330 driver genes, including 74 which are novel to any cancer. Across all cancer types 16% of the patients are eligible for a currently approved therapy. Computational chemogenomic analysis of cancer mutations identified 96 additional targets of compounds that are potentially active and represent candidates for future clinical trials, expanding opportunities for improved patient care. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding was provided by the Wellcome Trust (214388), Cancer Research UK (C1298/A8362) and the Medical Research Council. A.S. is in receipt of a National Institute for Health Research (NIHR) Academic Clinical Lectureship, funding from the Royal Marsden Biomedical Research Centre, a starter grant for clinical lecturers from the Academy of Medical Sciences, and is recipient of the Whitney-Wood Scholarship from the Royal College of Physicians. This is a summary of independent research supported by the NIHR Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research. This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: HRA Committee East of England of Cambridge South gave ethical approval for this work (REC Ref 14/EE/1112). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data is available through the Genomics England Platform.