a, Principles of timing mutations and copy number gains based on whole-genome sequencing. The number of sequencing reads reporting point mutations can be used to discriminate variants as early or late clonal (green or purple, respectively) in cases of specific copy number gains, as well as clonal (blue) or subclonal (red) in cases without. b, Annotated point mutations in one sample based on VAF (top), copy number (CN) state and structural variants (middle), and resulting timing estimates (bottom). LOH, loss of heterozygosity. c, Overview of the molecular timing distribution of copy number gains across cancer types. Pie charts depict the distribution of the inferred mutation time for a given copy number gain in a cancer type. Green denotes early clonal gains, with a gradient to purple for late gains. The size of each chart is proportional to the recurrence of this event. Abbreviations for each cancer type are defined in Supplementary Table 1. d, Heat maps representing molecular timing estimates of gains on different chromosome arms (x axis) for individual samples (y axis) for selected tumour types. e, Temporal patterns of two near-diploid cases illustrating synchronous gains (top) and asynchronous gains (bottom). f, Left, distribution of synchronous and asynchronous gain patterns across samples, split by WGD status. Uninformative samples have too few or too small gains for accurate timing. Right, the enrichment of synchronous gains in near-diploid samples is shown by systematic permutation tests. g, Proportion of copy number segments (n = 90,387) with secondary gains. Error bars denote 95% credible intervals. ND, near diploid. h, Distribution of the relative latency of n = 824 secondary gains with available timing information, scaled to the time after the first gain and aggregated per chromosome.