Aberrant DNA Methylation in Cutaneous Malignancies

In recent years it has become evident that in addition to genetic mutations also epigenetic alterations are causally related to the development and progression of cancer. The epigenetic mechanism most relevant in the pathogenesis of cancer appears to be aberrant methylation of tumor-suppressor gene promoters associated with transcriptional downregulation. Malignancies arising in the skin are the most prevalent in humans. The most common are basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), melanoma, and cutaneous lymphoma. The visibility and accessibility of cutaneous tumors facilitate the scientific study of sequential epigenetic alterations occurring during tumorigenesis and might make treatment of malignant skin lesions using locally applied demethylating agents possible. In this review, we summarize the current knowledge concerning alterations of DNA methylation in BCC, SCC, melanoma, and cutaneous lymphoma. Furthermore, the potential “epigenotoxic” effects of ultraviolet radiation, an environmental carcinogen implicated in the tumorigenesis of most cutaneous malignancies, will be discussed. From the limited number of investigations of promoter hypermethylation in cutaneous malignancies, it is already clear that a great number of potential tumor-suppressor genes are epigenetically silenced in skin cancer, including components of signaling pathways critical in the pathogenesis of these malignancies.