ESR1 and Familial prostate cancer: Within hypermethylated c-HMRs, we detected previously reported frequent DNA hypermethylation at gene promoters such as MGMT in glioblastoma, NSD1 in neuroblastoma, ESR1 in breast cancer, GSTP1 in prostate cancer and the promoter hypermethylation of RASSF1 in various cancer contexts (Figure 4d, Supplementary Figures S16a–d).