Differences in Degree of DNA Methylation Separate Melanocytes from Melanomas

Cancer researchers used advanced gene mapping techniques to detect chemically modified (methylated) DNA in melanoma cells and identified a number of genetic markers that may enable development of directed therapy against the disease.

DNA methylation is the main epigenetic mechanism for controlling gene expression. Mistakes resulting in too much (hypermethylation) or too little (hypomethylation) methylation of the DNA are characteristics of some disease states, including some cancers.

Investigators at Yale University (New Haven, CT, USA) used advanced gene mapping techniques to determine the genome-wide distribution of methylated DNA in normal melanocytes and in melanomas.

They reported in the June 29, 2009, online edition of the journal Genome Research that the pattern of methylation differed between the normal and cancer cells in 76 gene promoter regions. In the cancer cells, 68 of the promoters were hypermethylated and 8 were hypomethylated as compared to the normal cells. Promoter methylation and differential gene expression of five markers (COL1A2, NPM2, HSPB6, DDIT4L, MT1G) were validated by sequencing of bisulfite-modified DNA and real-time reverse transcriptase PCR, respectively. The incidence of promoter methylation increased moderately in early and significantly in advanced-stage melanomas.

The authors summed up their report by saying, "Our approach allows robust identification of methylation markers that can be applied to other studies involving genome-wide promoter methylation. In conclusion, this study represents the first unbiased systematic effort to determine methylation markers in melanoma and revealed several novel genes regulated by promoter methylation that were not described in cancer cells before."

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