In addition to the recent discoveries of mutations in enzymes that regulate DNA methylation, early observations in multiple myeloma showed promoter DNA hypermethylation and gene silencing of the cyclin-dependent kinases inhibitors CDKN2B (p15) and CDKN2A (p16), suggesting they were incapable of preventing cell cycle progression (153). Here, CDKN2A is linked to plasma cell myeloma.