(A) Workflow of study and data analysis. Tumor specimens (gray) from both primary prostate cancer and mCRPC were included in this study. Linked-read and short-read WGS and RNA-Seq data sets were either generated for this study or reanalyzed from prior studies (9, 33). An overview of the genomic alteration and characterization analysis is shown. (B) Clinical annotations and somatic alterations for 143 patient samples in the pooled mCRPC cohort. Samples are ordered by treatment type; the 4 patients with pretreatment and post-progression pairs are placed at the right. Top: Clinical and sample information and genomic pattern classifications, including neuroendocrine prostate cancer (NEPC) and androgen receptor pathway active prostate cancer (ARPC). Middle: Distribution of genomic rearrangement types in individual samples. Bottom: Mutational burden for SNVs and indels computed as number of mutations per mega–base pair (Mb). Y axis shown in logarithmic scale. Threshold lines indicate mutational burden at 2.5 and 5 mutations per Mb. (C) Genomic rearrangement alteration profiles of key mCRPC genes. Top: Events were categorized into gene transecting or gene flanking based on the overlap of breakpoints with the gene body and flanking 1 Mb of either the transcription start site or the termination site of the gene. Only 159 genes reported and known to be involved in prostate cancer were considered in this analysis (Supplemental Table 1, G and H). Middle: Frequency and distribution of rearrangement types for gene transecting events; genes with ≥10% frequency are shown. Gene transecting events were prioritized over flanking events during annotation. The category “Multiple” represents gene-sample pairs carrying more than 1 type of rearrangement event. Bottom: Frequency of gene flanking events by tandem duplication; genes with ≥10% are shown.