In a
cancer genome, the noncoding sequence contains the vast majority of somatic mutations. While very few are expected to be
cancer drivers, those affecting regulatory elements have the potential to have downstream effects on gene regulation that may contribute to
cancer progression. To prioritize regulatory mutations, we screened somatic mutations in the Pan-
Cancer Analysis of Whole Genomes cohort of 2,515
cancer genomes on individual bases to assess their potential regulatory roles in their respective
cancer types. We found a highly significant enrichment of regulatory mutations associated with the deamination signature overlapping a CpG site in the
CCAAT/Enhancer Binding Protein β recognition sites in many
cancer types. Overall, 5,749 mutated regulatory elements were identified in 1,844
tumor samples from 39 cohorts containing 11,962 candidate regulatory mutations. Our analysis indicated 20 or more regulatory mutations in 5.5% of the samples, and an overall average of six per
tumor. Several recurrent elements were identified, and major
cancer-related pathways were significantly enriched for genes nearby the mutated regulatory elements. Our results provide a detailed view of the role of regulatory elements in
cancer genomes.