Somatic mutations of 858 tumors from 22 cancer types were downloaded from the supplementary information of Weinhold et al.5 Hypermutated tumors with more than 200,000 mutations were excluded from the analysis. Cancer types with less than ten samples were excluded from the analysis. For CBS mutation rate calculation in Fig. 6b, CBSs were defined as CTCF motifs overlapping a CTCF ChIP-seq peak in at least one ENCODE cell line. We further defined tissue-specific CBSs for 14/19 cancer types for which DNaseI profiles in the matched tissue types are available in Roadmap Epigenomics. Tissue-specific CBSs were defined as generic CBSs that fall under DNaseI peaks in the respective tissue. Supplementary Figure 15 shows the mutation rates at tissue-specific CBSs.