Hypermethylation in human cancers of the RIZ1 tumor suppressor gene, a member of a histone/protein methyltransferase superfamily

The retinoblastoma protein-interacting zinc finger gene RIZ1 is a tumor sup pressor gene and a member of a nuclear histone/protein methyltransferase su perfamily. RIZ1 inactivation is commonly found in many types of human cance rs and occurs through loss of mRNA expression, frame-shift mutation, chromo somal deletion, and missense mutation. RIZ1 is also a tumor susceptibility gene in mice. We now show that loss of RIZ1 mRNA in human cancers is associ ated with DNA methylation of its promoter CpG island. Methylation of the RI Z1 promoter strongly correlated with lost or decreased RIZ1 mRNA expression in breast, liver, colon, and lung cancer cell lines as well as in liver ca ncer tissues. Treatment with the methylation inhibitor 5-aza-2'-deoxycytidi ne activated RIZ1 mRNA expression in cancer cells. Furthermore, methylation was found in 11 of 25 (44%) breast cancer specimens and 20 of 32 (62%) liv er cancer specimens. Our results suggest that DNA methylation is a common m echanism in inactivating the RIZ1 tumor suppressor gene in human liver and breast cancers.