SPDEF and prostate neoplasm: Moreover, we observed that high Gleason-grade prostate tumors have higher levels of DNMTs (DNMT1, DNMT3A, and DNMT3B) and frequently contain highly methylated CpG sites within the SPDEF gene. In addition, our findings indicate that the CpG islands of the SPDEF gene are hypermethylated in CRPC cell lines.