Fig. 4.

Androgen receptor alterations. Comprehensive profiling of AR was performed in 275 cell-free DNA samples from 177 mCRPC patients. a The upper panel displays the circulating tumor DNA fraction. The dashed lines at 0.02, 0.10, and 0.20 denote the cutoffs to reliably detect point mutations, loss of heterozygosity, and homozygous deletions, respectively. Bottom panel, heatmap of the mutational landscape detected in the androgen receptor from circulating tumor DNA profiling. Type of alteration is coded according to the bottom legend. For visualization purposes, only samples with an alteration are shown here (126 samples from 89 individuals). Up to two mutations or structural variants (forward and backslashes) are displayed per sample. X-axis: cell-free DNA samples sorted according to the number of alterations detected. Patients with multiple samples are colored in blue. The asterisk indicates samples with microsatellite instability. b The fraction of patients with alterations in the androgen receptor is categorized by type of alteration and line of therapy. Only high-impact mutations, e.g., hotspot mutations, are shown here. Intra-AR structural variation is colored according to the legend in a. The rightmost bar plot represents the fraction of patients with any alteration in the androgen receptor. Abbreviations: mCRPC[number], metastatic castration-resistant prostate cancer and line of therapy; _B, baseline; Nbr, number of samples profiled