Extended Data Fig. 15: Overview of estimations of promoter activity and non-coding promoter mutations associations and patterns.

a, b, The technical variation of the promoter activity estimates across varying library depth (a) and positional bias (b). c, The number of outlier promoters per tumour type according to promoter activity variance (variance larger than 1.5 × the interquartile range). d, Distribution of promoter mutations around promoters across the PCAWG cohort for major, minor and inactive promoters. Red lines indicate the window 200-bp upstream of a TSS, in which major promoters show an enrichment of mutations whereas minor and inactive promoters do not. e, Distribution of promoter mutations around promoters for the top two most mutated types of cancer (skin melanoma and colorectal adenocarcinoma (ColoRect–AdenoCA)). Colorectal adenocarcinoma displays a very different mutational pattern from other types of cancer. f, Distribution of promoter mutations around major, minor and inactive promoters across several types of cancer. Red lines indicate the window 200-bp upstream of a TSS, in which major promoters show an enrichment of mutations whereas minor and inactive promoters do not. g, Schematic of the calculation of non-coding promoter mutational burden. h, Overview of non-coding promoter mutations per sample and the number of mutated promoters per tumour type for promoters with at least three mutated samples. i, j, Association of absolute (i) and relative (j) promoter activity with promoter mutations across all samples. k, l, Overview of promoter mutations for skin melanoma tumours. k, Most promoter mutations are C>T, which indicates UV-induced DNA damage. l, Distribution of promoter mutations for each mutation class reveals the enrichment of C>T mutations around the 200-bp window upstream. m, n, Overview of promoter mutations for colorectal adenocarcinoma tumours. m, Most promoter mutations are C>A and C>T. n, Distribution of promoter mutations for each mutation class does not display an enrichment of mutations around the 200-bp window upstream, differing from the mutation pattern of skin melanoma tumours.