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 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.

Whole genome sequencing reveals differences in the genetic landscape of interval and screen-detected breast cancer

“…Considering hormone receptor status, we con ned our analysis to ductal histology since no patients with triple negative (TN) tumours had lobular breast cancer. (iv) removed insertions and deletions within 10bps of a common germline indel (Supplementary Methods) 15 Driver gene identi cation…”