Abstract
Methylation of DNA is known to be an important mechanism of gene regulation. A hallmark of cancer is the deregulation of the DNA methylation machinery and aberrant DNA methylation patterns 1. In vertebrate genomes, a large fraction of the CG dinucleotide sequence is modified by methylation in gene- and tissuespecific patterns 2. Methylation of critical regulatory regions silences gene expression; loss of methylation is associated with gene activation 3. Because cancer progression requires many changes in the normal program of gene expression, it stands to reason that aberrations in DNA methylation play a critical role in the changes in gene expression involved in cancer progression and metastasis. Methylation changes in DNA play a role very similar to that of genetic mutations in cancer; however, unlike a genetic alteration, DNA methylation is potentially reversible with pharmacologic intervention. The DNA methylation machinery was therefore proposed—almost a decade and a half ago—to be an attractive anticancer target 4.
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