Furthermore, after reactivation following genetic knockout of DNMT1 and DNMT3B in a colon cancer cell line, CDKN2A is silenced before DNA hypermethylation is re-established [103] and CDNK2A silencing also occurs prior to hypermethylation in colonies of human mammary epithelial cells (HMECs) that escape replicative arrest in culture [104]. Here, CDKN2A is linked to malignant colon neoplasm.