Fig. 3

Darwinian evolution mainly shapes ITH in PCRC. The multiregion mutation profiles of the ten PCRCs were compared with those of eight non-hypermutated ACRCs; these ACRCs in our previous study led us to conclude that ITH was mainly generated by neutral evolution. a Distribution of driver genes. Colored tables show the presence of trunk (orange) or branch (green) mutations on known driver genes in each case of the PCRCs and ACRCs. If a case had multiple driver mutations, the number is provided within the corresponding cell. Top and right bar graphs represent the sums of driver mutations for each sample and each driver gene, respectively. b Bar plots showing the proportions of trunk mutations versus branch mutations on driver mutations. Significant enrichment of branch mutations on driver genes in PCRC (25/51) was compared with ACRC (10/45; P = 0.010; Fisher’s exact test). c Comparison of VAFs for trunk, internal branch (int-Br), and external branch (ext-Br) mutations. Hierarchical Bayesian analysis was employed to correct the effects of tumor content and read depth as well as to remove the residuals associated with individual mutations, samples, and cases (see Methods and Supplementary Fig. 17). The density plot shows an estimated posterior distribution of the corrected mean VAFs for trunk mutations, int-Br mutations, and ext-Br mutations in PCRC or ACRC. PCRC harbored int-Br mutations with higher VAFs than ACRC. 95% CI 95% credible interval