Taken together, profiling of late stage CRPC with a broad panel of lineage markers documents that (a) YAP1 loss generally occurs in ASCL1–positive NEPC tumors, (b) TROP2 is predominantly expressed in PRAD/HGC, whereas DLL3 is almost exclusively present in NEPC tumors, (c) in comparison to ASCL1, the expression of other transcription factors linked with neuroendocrine phenotypes, such as NEUROD1 and POU2F3, is less common, and (d) SYP expression alone has limitations as a diagnostic marker for NEPC. This evidence concerns the gene DLL3 and prostate adenocarcinoma.