Identifying The Molecular And Environmental Factors Mediating Transformation Of Melanocyte Stem Cells To Melanoma.

Cutaneous melanoma is the most lethal form of skin cancer. However, the molecular mechanisms and environmental factors that can promote melanoma initiation and development from skin without an identified precursor lesion are not well defined. In these studies, we found that proinflammatory stress induced by environmental factors such as ultraviolet radiation can generate a sufficient stimulus to induce melanoma initiation from melanocyte stem cells (McSCs) containing Braf and Pten mutations. Moreover, our data demonstrate a role for the nonhistone architectural chromatin factor Hmga2 as an important molecular mediator in the induction of inflammation in murine skin following UVB (ultraviolet B) exposure. Our findings show a reduced recruitment in immune cell populations to the skin after UVB irradiation. Taken together, these data demonstrate that McSCs are sufficient to act as melanoma cells of origin and that UVB-induced inflammation acts to accelerate tumor initiation. Understanding the underlying factors that can cause melanoma initiation can provide valuable insight for melanoma prevention and control. This abstract is also being presented as Poster A03. Citation Format: Hyeongsun Moon, Leanne R. Donahue, Jerry Zhu, Andrew C. White. Identifying the molecular and environmental factors mediating transformation of melanocyte stem cells to melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr PR08.