Early Detection Research Network


It is suggested that the increased levels of plasma AdoMet, or s-adenosylmethionine, in lung cancer patients relate to the role of AdoMet in DNA methylation. Hypermethylation of gene promoter regions is associated with silencing of transcription. Methylation of pyrimidines in DNA is a postreplicative event leading to the formation of 6-methylcytosine from cytosine. A family of three enzymes (the cytosine-DNA methyltransferases) catalyzes methylation of the fifth position of the cytosine ring, using AdoMet as the donor molecule. When this occurs within a CpG island located in the promoter region of a gene, it is accompanied by changes in chromatin composition around the island. These changes may deny access to regulatory proteins needed for transcription, or methylation may serve as a recognition mechanism for DNA/protein interactions.11,13 For example, the expression of several tumor suppressor genes (including p16, FHIT, RASSF1, SEMA3B, E-cadherin, DAP kinase, and others) is turned off by promoter methylation.
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