Cancer driver genes and opportunities for precision oncology revealed by whole genome sequencing 10,478 cancers

Abstract Identifying cancer driver genes is key for delivering the vision of precision oncology. The falling cost of whole genome sequencing (WGS) potentially makes WGS an attractive single all-encompassing test to identify cancer drivers in a patient, which may not be captured by standard panel testing but are targetable by small molecules. We analysed WGS data on 10,478 patients 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 would be 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.