TP53 and cancer: Among the remaining 24 MDGs that are potentially new “epigenetic modulators”, 12 are associated with genome-wide methylation changes in more than one cancer type (Table 1), including TP53, PTEN, RB1, NF1, CTNNB1, HRAS, BRAF, IDH1, NRAS, RNF43,ZBTB20, and CDH1. To focus on pan-cancer effects, we worked on only these 12 driver genes that are associated with genome-wide methylation changes in more than one cancer types.