Consecutive CGP results were reported for 3,476 unique patients with
prostate cancer by prospective sequencing (median coverage, 743×) of tissue
samples using a validated assay16 (link)(FoundationOne; Foundation Medicine, Cambridge, MA; Appendix Table A1). For patients with multiple samples, the sample with
the highest sequencing quality metrics was included. Age and site of specimen
collection were abstracted from accompanying pathology reports, clinical notes, and
requisition forms. The pathologic diagnosis of each case was confirmed on routine
hematoxylin and eosin-stained slides. Results were analyzed for GAs and gene
signatures (TMB, MSI, genome-wide loss of heterozygosity [gLOH]). Germ-line/somatic
mutation calls were predicted without a matched normal; in validation testing of 480
tumor-only sequencing calls against matched normal samples, accuracy was 95% for
somatic and 99% for germline calls.17 (link) Enrichment was defined as the difference in GA frequency
between metastatic and primary sites. Potentially targetable GAs were defined by
European Society for Medical Oncology Scale for Clinical Actionability of Molecular
Targets criteria.18 (link) The Appendix
provides additional details on the methods used in this study.