Differential hypomethylation of known regulatory elements such as the DNA replication initiation site located in the first intron of DNMT1 gene (A-8 HMR) [49] and the estrogen receptor binding sites within intron 2 of SLC22A5 (B-5 HMR) [50] were also observed in tumor cells (S9C and D Fig). This evidence concerns the gene ESR1 and neoplasm.