(A) Mutation and copy number alteration (CNA) status for selected genes with recurrent alterations in metastatic prostate cancer across LNCaP strains. The bottom right triangle indicates an observed pathogenic mutation (SNV/INDEL) within the gene, and the top left triangle indicates CNA status (amplification, shallow deletions, deletions, deep deletions) that overlap the gene. CNA events that also have loss of heterozygosity (LOH) status are depicted with a hatch pattern. “Multiple” indicates instances where 2+ pathogenic mutations are observed for that gene. Tumor mutation burden was computed as the number of nonsynonymous mutations per megabase pairs of coding regions (top). Aneuploidy status (arm gain, arm deletion) is indicated for select chromosome arms. Fusion status indicates evidence for genomic rearrangement involving an ETS transcription factor. Genes that have been transected by at least 1 of 2 breakpoints of a structural variation (SV) event are indicated with a black border around the triangle. (B) Genome-wide integer copy number profiles generated by TitanCNA. Data points represent individual germline heterozygous SNPs or 10 kb pair-sized bins. Estimated integer copy number (y axis) is indicated by colors: deletions (green), copy neutral (blue), gain (dark red), and amplifications (bright red). (C) Cell-lineage tree reconstruction based on inferred subclonal composition using all unique pathogenic SNV mutations (24,282) across the substrains. SNVs included in the analysis had filtering criteria of presence in COSMIC Gene Census; deleterious status by SIFT, LRT, MutationTaster, FATHMM, and ClinVar; 1% or less in gnomAD or ExAC databases; and 10 or more total reads and 3 or more mutant reads in the tumor. PyClone-VI was used to determine cellular prevalence and clonal clusters; LICHeE for lineage reconstruction; cloneMap for visualization. INDEL, insertions/deletions; SNV, single nucleotide variant.