We have identified a hypermethylation defect in a subset of human breast cancer cell lines and primary breast cancers that are characterized by DNMT hyperactivity, overexpression of DNMT3b, and concurrent methylation-dependent silencing of numerous genes (including CDH1, CEACAM6, CST6, ESR1, GNA11, MYB, MUC1, SCNN1A and TFF) (10). The gene discussed is ESR1; the disease is breast cancer.