Promoter hypermethylation of DLC-1, a candidate tumor suppressor gene, in several common human cancers.

Aberrant methylation of CpG islands within the promoter regions of tumor suppressor or cancer-related genes is a common mechanism leading to the silencing of gene expression. To determine whether aberrant methylation is a contributing factor to transcriptional inactivation of DLC-1 (deleted in liver cancer-1), a candidate tumor suppressor gene, we examined its methylation status in twelve hepatocellular carcinoma. breast, colon, and prostate tumor cell lines with low or undetectable expression of DLC-1. By Southern blot analysis of DNA digested with the methylation sensitive enzyme HpaII, we found a different degree of promoter hypermethylation in all cell lines with aberrant DLC-1 expression. The hypermethylation status was reversed by the addition of 5-aza-2'-deoxycytidine, a demethylating agent, in one human hepatocellular carcinoma line. These observations suggest that hypermethylation is responsible for abrogating the function of the DLC-1 gene in a subset of liver, breast, colon, and prostate cancers.