Intraprimary heterogeneity analysis based on 96 samples from 38 subjects (13 ovarian86, 10 colorectal23,79,87,88, 9 breast78, 4 pancreatic64, 1 gastric89, and 1 endometrial cancers13; Supplementary Methods S1). Intermetastatic heterogeneity analysis based on 67 metastases samples of 17 subjects (6 pancreatic64, 4 endometrial13,104, 3 colorectal79, 2 breast103, 1 gastric89, 1 prostate105 cancers). a | Driver gene mutations present in all samples from a single primary tumor were more frequently predicted to be functional than those present in only a subset of the samples from a primary tumor (54% vs. 11%, P < 0.001). The fraction of subclonal functional driver gene mutations (11%) was not significantly different from the fraction of clonal or subclonal functional passenger gene mutations in the same tumor (3.3% and 2.3%). b | Mutations in driver genes that were present among all metastases samples of a subject were more frequently predicted to be functional than those present only in a subset of metastases samples (65% vs. 0%, P < 0.001). The fraction of subclonal functional driver gene mutations (0%) was not significantly different from the fraction of clonal and subclonal functional passenger gene mutations in the same samples (4.1% and 6.6%). c | On average 69% and 66% of the mutations per patient were clonal (homogeneous) among primary tumor samples and among metastases, respectively. Mutations in putative driver genes were significantly more homogeneous among primary tumor samples (90%, P < 0.001) and among metastases (84%, P < 0.0048) than mutations in all genes (sum of passenger genes and driver genes). Likely functional driver gene mutations were even more homogeneous among primary tumor samples (98%, P < 0.0042) and among metastases (100%, P < 0.0018) than other categories of mutations. Two-sided Fisher’s exact tests were used in panels a and b. Two-sided Wilcoxon rank-sum tests were used in panel c. Thick black bars denote 90% confidence interval. Numbers in brackets denote number of variants in each group. ** P < 0.01; *** P < 0.001.