Most analyses of cancer genomes to date have focused on characterizing somatic variants in protein-coding regions. We intersected four available whole-genome cancer datasets with ENCODE annotations (Figure 9C, Supplementary Figure L2). Overall somatic variation is relatively depleted from ENCODE annotated regions, particularly for elements specific to a cell type matching the putative tumor source (e.g., skin melanocytes for melanoma). Examining the mutational spectrum of elements in introns for cases where a strand-specific mutation assignment could be made reveals that there are mutational spectrum differences between DHSs and unannotated regions (0.06 Fisher’s Exact, Supplementary Figure L3). The suppression of somatic mutation is consistent with important functional roles of these elements within tumor cells, highlighting a potential alternative set of targets for examination in cancer.
