UV-Induced Epigenetic Field Effect as a Target for Melanoma Therapy and Prevention
Abstract
Cutaneous malignant melanoma is a complex, aggressive, and highly chemoresistant cancer that arises from the pigment producing melanocyte cells located within the skin. It has a high mutational burden associated with exposure to ultraviolet radiation (UVR). UV- induced DNA mutations (C>T) are incontrovertibly linked to the disease; however, the most common mutations found in both nevi and melanoma (i.e. BRAFV600E and NRASQ61L/R) do not bear UV-signaturemutations. It is unclear if these are initiators or selected for during disease progression highlighting our lack in knowledge of the critical molecular targets in theinitiation of UV-induced melanoma. We propose an alternative hypothesis that UV-driven epigenetic reprograming of a field of melanocytes (or an epigenetic field-effect) proceeds and complements subsequent DNA mutations in the progression of melanoma. We aim to understand the involvement of these proposed epigenetic changes in the underlying molecular mechanisms of UV-induced melanoma. This would be the first evidence epigenetic alterations from UV-induced stress in mammalian cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2017
- Accession Number
- AD1050183
Entities
People
- M. R. Zaidi
Organizations
- Temple University