(A) Copy number of AR gene and its enhancer (~624 kb upstream) for mCRPC cohort samples after adjustment by tumor purity and sample ploidy normalization. Data shown for samples with available AR gene expression data. Left: Copy number of AR and its enhancer is shown in log₂ scale, colored based on AR gene expression level (transcripts per million [TPM]). Right: Excerpt of figure highlighting AR expression for samples with lower copy number values. (B) AR expression for AR locus copy number status for 122 samples with available AR gene expression data. ANCOVA test was performed to account for tumor purity and ploidy as covariates. Tukey’s HSD P values for pairwise comparisons between groups with AR locus amplification status and groups with no amplification. (C) Patterns of rearrangements involving the AR locus in 143 mCRPC samples. Presence of specific alteration events and complex rearrangements (black) was predicted automatically and manually curated. AR gene expression shown (blue shades) for the same samples in B; samples with no available expression data are indicated in gray. (D–H) Representative examples of each category. Complex and simple rearrangement patterns involving the AR locus, including focal duplication events on AR enhancer (D), intragenic amplification event leading to a breakpoint within AR between exons 4 and 5 (E), chromosome-level chromothripsis events involving AR and enhancer (F), arm-level chromothripsis coinciding with AR amplification by break-fusion-break cycle (G), and extrachromosomal DNA amplicon including AR and enhancer (H). AR gene boundary (green) and its enhancer (yellow) are shown. Concave arcs, intrachromosomal SV events; convex arcs, interchromosomal SV events. Copy number values represent 10 kb bins and have been tumor purity corrected.