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MC1R CpG island regulates MC1R expression and is methylated in a subset of melanoma tumours.

Melanocortin 1 receptor (MC1R) is a G protein-coupled receptor expressed in melanocytes where it plays an important role in skin pigmentation and the UV response, and has implications in melanoma development. Here we show that methylation of a CpG island (CGI) within the MC1R gene can control expression of MC1R in melanoma. This CGI overlaps with a potential enhancer region, and is unmethylated in normal melanocytes but highly methylated in other skin cells, suggesting a melanocyte specific function. Analysis showed that MC1R was the only gene significantly differentially expressed by methylation of this region. Within several data sets, this region is methylated in a subset of melanoma tumours (55-74% of tumours) and results in reduced MC1R expression and significantly longer overall survival. This article is protected by copyright. All rights reserved.

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