Silencing of genes by promoter hypermethylation: key event in rodent and human lung cancer

Transcriptional silencing by CpG island hypermethylation has become a critical component in the initiation and progression of lung cancer. The ability of pharmacologic agents to reverse promoter hypermethylation also makes it an attractive target to pursue for prevention of lung cancer. Animal models, together with studies in humans have fostered significant advances in elucidating the role of gene-specific methylation in cancer initiation and progression, the modulation of promoter methylation by carcinogen exposure and the ability to block tumor development by preventing epigenetically mediated gene silencing. These advances represent the beginning of efforts to develop a progression model for lung cancer that should aid efforts for early detection and gene targeting for therapy, and the development of preventive interventions that reverse epigenetic-mediated gene silencing.