Tumor specimens were obtained prospectively through clinical protocols approved by the Weill Cornell Medicine (WCM) Institutional Review Board (IRB) with informed consent (IRB #1305013903, #1210013164) or retrospectively (IRB #0905010441) and germline DNA obtained from either peripheral blood mononuclear cells (PBMCs) or benign tissue. The total number of subjects enrolled in this study was 81, all of male gender; no blinding, randomization, or exclusion criteria were used. All fresh/frozen tissues were processed as previously described26 (link),52 (link). All hematoxylin and eosin stained slides were reviewed by board-certified pathologists (J.M.M., M.A.R.). Tumors were classified based on histomorphology as adenocarcinoma (A) or CRPC-NE (B-E) based on a published pathologic classification system8 (link) (Supplementary Fig. 1). Category A represents usual prostate adenocarcinoma without neuroendocrine differentiation, Category B represents usual prostate adenocarcinoma with neuroendocrine differentiation > 20%, Category C represents small cell carcinoma, Category D represents large cell neuroendocrine carcinoma, and Category E represents mixed small cell carcinoma – adenocarcinoma. Clinical and pathologic features of the cohort are summarized in Supplementary Table 1 and Supplementary Fig. 1.