Genetic factors linked to high-risk prostate cancer and the development of NEPC include the loss of tumor suppressors RB1 and TP53, amplification of cell-cycle regulator Aurora Kinase A and MYCN, splicing of transcriptional repressor REST by SRRM4, increased expression of PEG10, and neural transcription factors, as well as prostate cancer cell lineage plasticity inducers BRN2 and ASCL15,7–16. This evidence concerns the gene RB1 and Familial prostate cancer.