Extended Data Fig. 5: Mutational processes of clustered driver events.

a, The percentage of clustered driver substitutions and indels within each cancer type. All samples 2,583 whole-genome sequenced samples from PCAWG with a detected driver event are included; however, cancer types with fewer than 10 samples are not presented. b, The proportion of clustered driver mutations per cancer gene compared between oncogenes (n = 19 genes) versus tumour suppressor genes (n = 30 genes) and genes with high numbers of isoforms (n = 17) versus genes with low numbers of isoforms (n = 23; upper and lower quartiles of isoforms across all cancer drivers). c, The proportion of clustered driver mutations for a given subclass per cancer gene compared between oncogenes (n = 17 genes with clustered substitutions and n = 13 with for clustered indels) versus tumour suppressor genes (n = 28 genes with clustered substitutions and n = 70 genes with clustered indels). d, The relative expression of driver genes containing clustered (copper) versus non-clustered events (green). All expression values were normalized using FPKM normalization and upper quartile normalization obtained from the official PCAWG release and were subsequently normalized using the average expression of the wild-type gene. A value of 1 (dashed lined) reflects no difference in expression compared to the wild-type gene. e, The proportional activity of mutational signatures contributing to clustered driver events within each subclass. MBSs did not contribute to any reported driver events. For analyses in b–d, p-values were generated using a two-tailed Mann–Whitney U-test (*P < 0.05; p = 0.03 for STAT6; p = 0.04 for CTNNB1; p = 0.02 for BTG1). For each boxplot, the middle line reflects the median, the lower and upper bounds of the box correspond to the first and third quartiles, and the lower and upper whiskers extend from the box by 1.5x the inter-quartile range (IQR).