There is an urgent need to improve approaches for cancer diagnosis and targeted treatment, which requires a detailed understanding of the disease and its genetic basis. The advent of next-generation sequencing has allowed researchers to obtain comprehensive profiles of acquired genetic mutations in patient tumors. However, due to primarily reasons of cost, these sequencing approaches have so far ignored mutations in the multitude of non-protein-coding DNA sequence elements that control and regulate gene expression, and strong evidence is currently accumulating that mutations in these regions can cause cancer.With recent improvements in DNA sequencing efficiency and cost, it is now becoming feasible for large research consortia such as The Cancer Genome Atlas (TCGA) to perform whole genome sequencing (WGS) in large cohorts of cancer patients. The proposed research project, “CancerGenomes”, aims to systematically detect and functionally characterize cancer mutations in non-protein-coding regulatory regions using WGS datasets from TCGA. Specifically, I will develop computational and statistical methodology for detecting and evaluating the functional impact of non-coding mutations. Using WGS data from more than 700 cancer genomes in >20 cancer types, I will derive a pan-cancer atlas of candidate functional non-coding mutations and analyze their impact on individual cancer genes, pathways and regulatory networks.The feasibility of the project will be guaranteed by the applicant’s strong background in cancer genomics and TCGA data analysis in synergy with the host group’s unique expertise in gene regulation and whole genome sequencing analysis. Ultimately, the discovery of new cancer driver mutations in non-coding regions can lead to new anti-cancer drug targets and more accurate diagnosis of cancer patients.