Abstract
<div>Abstract<p>Malignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified 17 genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2′-deoxycytidine. Eight of these genes have not been previously shown to undergo DNA methylation in any form of cancer. Three of the genes, <i>QPCT, CYP1B1</i>, and <i>LXN</i>, are densely methylated in >95% of uncultured melanoma tumor samples. Reexpression of either of two of the silenced genes, <i>HOXB13</i> and <i>SYK</i>, resulted in reduced colony formation <i>in vitro</i> and diminished tumor formation <i>in vivo</i>, indicating that these genes function as tumor suppressors in melanoma. (Cancer Res 2006; 66(23): 11187-93)</p></div>
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