<p>Mutational subtypes of localized prostate cancer. <b>A,</b> Mutation densities (rows) differ by ETS fusion and <i>NKX3-1</i> CNA status (columns). Dot size and color gives effect-size as a <i>Z</i>-score, scaled to ETS-negative, <i>NKX3-1</i>–neutral patients. The barplot on the right shows the FDR-adjusted <i>P</i> values from nonparametric Kruskal–Wallis tests. <b>B,</b> Comparison of log<sub>10</sub>-transformed SNV mutation rate for patients divided by ETS fusion and <i>NKX3-1</i> CNA status. <i>P</i> value is from a nonparametric Kruskal–Wallis test. <b>C,</b> Using a generalized linear model, eight driver mutations were identified whose frequency differed by ETS fusion and/or <i>NKX3-1</i> CNA status after FDR adjustment for multiple-testing. Dot size and color indicate the difference in proportion, scaled to patients with ETS-negative, <i>NKX3-1</i>–neutral tumors. Background grayscale represents <i>Q</i> values from a proportion test. <b>D,</b> Co-occurrence and associations of driver region pairs across 666 localized prostate tumors. For each pair of driver regions, a hypergeometric test was used to assess whether more mutations were detected than expected by chance alone (co-occurrence) or fewer (mutual exclusivity) after FDR adjustment for multiple-testing (<i>Q</i> < 0.05). The bottom-left heatmap shows all driver pairs; the dotmap on the top right provides effect sizes (dots) and <i>Q</i> values for a subset. Yellow stars on the heatmap mark drivers which are the same gene in clonal and subclonal CNAs. Dot size reflects the difference in driver events, quantified as the observed number minus the expected number. Color indicates deviation direction. The red circle signifies more driver events than expected by chance, whereas the upside-down blue triangle indicates fewer events than expected. <b>E,</b> Clustering of driver regions identifies seven patient subtypes: IMS1–IMS7. Columns are patients. The bottom set of rows shows clinical characteristics, the second set shows mutation densities, and the third shows driver mutations whose frequency differs between subtypes (proportion test; <i>Q <</i> 0.05). The top barplot gives the number of mutated driver regions for each patient. <b>F,</b> Summary subtype profiles showing the proportion of patients in the subtype with certain aberrations. In the positive direction, the proportion of clonal CNA gains, subclonal CNA gains, select GRs, and select SNVs. The lollipops show the proportion of patients for GRs and SNVs. In the negative direction, the proportion of patients in the subtype with clonal and subclonal CNA losses is shown. For each subfigure, CNAs in patients with subclonal PGA >80% were excluded. INV, inversions.</p>