Aberrant promoter DNA hypermethylation of tumor suppressor genes is a hallmark 
of cancer. This alteration is largely dependent on the action of de novo DNA 
methyltransferases (DNMTs) early during tumor progression, which supports the 
oncogenic role for these enzymes. However, recent research has identified 
several inactivating mutations of de novo DNMTs in various types of tumor. In 
addition, it has been shown that loss of de novo DNA methylation activity at 
advanced tumor stages leads to the promoter DNA demethylation-dependent 
expression of specific oncogenes. These new data support the notion that de novo 
DNMTs also have an important role in the maintenance of DNA methylation and 
suggest that, in addition to acting as oncogenes, they also behave as tumor 
suppressors. This potential dual role might have clinical implications, as DNMTs 
are currently considered bona fide targets in cancer therapy.