Extended Data Fig. 7: Phylogenetic tree topologies and metastatic dissemination patterns.

Evolutionary tree diagrams for all additional patients not provided in Fig. 6 and/or Extended Data Figure 8. Branch colors correspond to PyClone-identified clones, and to patient-specific matrices shown in Supplementary Fig. 7. Patients without metastatic clones shown had no available tumor fraction positive metastatic sample. a. Patients with evidence of multiple independent primary tumors. Localized independent tumors generally display less branching than metastatic lineages. b. Evolutionary trees of all other de novo mCSPC cases. Del: copy number deletion, mut: mutation (single-nucleotide substitution / small insertion or deletion). Equally parsimonious trees for ID17, ID18, ID29, and ID4 are shown in Supplementary Fig. 8e. c. Results for ID8 demonstrating heterogeneous mismatch repair defective status and extensive phylogenetic branching. Each shape (circle = primary, diamond = metastasis) is a Pyclone-identified clone assignment for each sample (n = 12), where shape size represents median cancer cell fraction of mutations within the cluster. MSH2/6 status is shown on the left. Mutations per megabase (Mut/Mb) of each sample are shown on the right and cluster mutation count is shown above. Colors are assigned to the truncal clone and phylogenetically distinct branches. d. Output from PyClone and SCHISM, colored by distinct branches, for ID8. Number of mutations per branch are annotated (branch length does not reflect mutation count). Each colored branch has a unique MSH2/6 status and Mut/Mb in associated samples. All samples with exclusively pink populations, including metastatic lymph nodes, are notably devoid of hypermutation and have intact MSH6, while the two other clusters (yellow and green) exhibit hypermutation and losses of both MSH2 and MSH6. The green clone likely contains a second hit not detectable by WES (for example intronic truncating rearrangement). All three populations colonized the metastatic niche. LR: log ratio, MLN: metastatic lymph node, PB: prostate biopsy, RP: radical prostatectomy, WDG: whole-genome duplication.