PTEN and Familial prostate cancer: Complex genomic changes underlying and regulating the progression of prostate cancer to CRPC and t-NEPC have been reported, such as deletion of tumor suppressors (RB1, TP53 and PTEN), activation of several transcription factors (BRN2, ASCL1, SOX2, N-Myc, and E2F1), and epigenetic remodeling (EZH2 and LSD1) [7, 26].