Abstract 2768: Global DNA hypomethylation is an important feature of melanoma

Abstract

Abstract Aberrant DNA methylation occurs nearly universally in cancer. Paradoxically, changes in DNA methylation are bi-directional: there is a focal increase in DNA methylation (hypermethylation), and a global overall decrease in DNA methylation (hypomethylation). Focal hypermethylation plays well described roles in silencing tumor suppressor genes in many malignancies, including melanoma. However, the functional role of global hypomethylation in tumorigenesis is relatively poorly understood. Melanoma is the deadliest form of skin cancer, accounting for approximately 74,000 new cases and 10,000 deaths in the United States in 2015. Changes in DNA methylation are also arguably one of the most common features of melanoma. Similar to other malignancies, most studies have focused on focal hypermethylation, identifying genomic loci differentially methylated between melanocytes and melanoma cells. However, global changes in DNA methylation have not been well described thus far. In this study, we describe global changes in DNA methylation in two melanoma clinical cohorts (JHH cohort, n = 13 nevi and n = 39 melanomas; NCI cohort n = 31 nevi and n = 97 melanomas) relative to benign nevi using a semi-quantitative immunohistochemistry based assay. We report a global decrease in DNA methylation levels in melanoma relative to benign melanocytic nevi consistent between both cohorts (p < 0.001, Student's t-test). Furthermore, we studied the functional effect of increasing the level of global DNA methylation in a panel of five early passage melanoma cell lines. Increases in global DNA methylation suppressed proliferation of melanoma cells (p <0.05, Student's t-test), and increased the proportion of apoptotic cells (p <0.01, Student's t-test). Global DNA hypomethylation is thus an important epigenetic feature of melanoma that may regulate proliferative capacity, and merits further investigation. Citation Format: Goran Micevic, Nicholas Theodosakis, Janis M. Taube, Marcus W. Bosenberg, Nemanja Rodic. Global DNA hypomethylation is an important feature of melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2768.