Extended Data Fig. 10: Stages of prostate tumour development.

a, Clonal architecture and its frequency in prostate cancer between Africans and Europeans. Tumours are divided into three groups: monoclonal, linear and branching polyclonal. The number of small somatic mutations (SSM) and CNAs as percentage of genome alteration (PGA) is provided as median and range in bracket. Cancer cell fraction (CCF) in each clone and/or subclone is shown in a circular node. Tumours that show characteristics consistent with being polytumours or with multiple independent primary tumors are excluded to remain conservative. b, Unbiased hierarchical clustering of CNAs between clonal (trunk) and subclonal (branch) mutations. Trunk mutations encompass those that occur between the root node (normal) and its only child node, while all others are classified to have occurred in branch. Red indicates gain; blue indicates loss; and rows indicate patients. Unidentified regions in trunk and branch are assumed to have neutral copy number. ConsensusClusterPlus showed seven CNA clusters among our patients to be optimal. The figure shows that a trunk alteration from one patient is mutationally similar to a branch alteration from another, rather than to other trunk ones from different patients in a cohort. c, Cancer timelines of GMS-B and -D identified in this study. Detailed explanation is provided in Fig. 5. Significant somatic interactions based on Fisher’s Exact test are indicated by odds ratio (OR) estimates and two-sided P-values on the top left panels. Interaction significance between somatic events in GMS-B and -D has P-values ranging from 3.16e-22–0.041 and 9.11e-25, respectively. Mutation rate plots show the median ±2× standard error of fitted data as dashed lines and error bands, respectively. d, Relative ordering model (PhylogicNDT LeagueModel) results for a cohort of 66 samples. The samples can be analysed if they have somatic events of interest prevalent greater than 5% of the sample size and have informative clonal status available for each event (16 events). Probability distributions show the uncertainty of timing for specific events in the cohort. e, Molecular timing distribution of copy number gains and loss of heterozygosity (LOH) between Africans and Europeans. Pie charts depict the distribution of the inferred mutation time for a given copy number alteration. Orange denotes early clonal gains/LOH, with a gradient to green for late gains/LOH. The size of each chart is proportional to the recurrence of this event across different patients. Most of the gains and LOH are considered early clonal based on MutationTimeR results. Whole-genome duplication is more frequent in Africans (63%) than in Europeans (57%).