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CD4+ T cells Reject Benign Melanocytic Nevi

ABSTRACT: CD4+ T cells Reject Benign Melanocytic Nevi

PROVIDER: PRJNA642297 | ENA |

REPOSITORIES: ENA

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CD4+ T cells Reject Benign Melanocytic Nevi

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Genome-scale DNA methylation analysis identifies repeat element alterations that modulate the genomic stability of melanocytic nevi

Project description:Acquired melanocytic nevi grow and persist in a stable form into adulthood. Using genome-wide methylation profiling, we evaluated 32 histopathologically confirmed, and dermoscopically characterized nevi, with matched adjacent skin, to identify key epigenetic regulatory mechanisms involved in nevogenesis. Benign (n=13; 69% globular and 31% non-specific dermoscopic pattern) and dysplastic (n=19; 95% reticular/nonspecific dermoscopic pattern) nevi were dissimilar with only two shared differentially methylated (DM) loci. Relative to adjacent skin, benign nevi demonstrated an increase in both genome-scale methylation and methylation of Alu/LINE-1 retrotransposable elements, a marker of genomic stability, as well as global methylation. In contrast, dysplastic nevi showed evidence for genomic instability via hypomethylation of Alu/LINE-1. The difference in methylation between benign and dysplastic nevi was statistically significant for Alu (P = 0.00019) and LINE-1 (P = 0.000035) retrotransposable elements. Using dermoscopic classifications, reticular/nonspecific nevi had 59,572 CpG DM loci (Q < 0.05), whereas globular nevi had non-significant DM loci. The relative activity of reticular/non-specific nevi was evidenced by 50,720 hypomethylated loci being enriched for accessible chromatin, and 8,852 hypermethylated loci strongly enriched, for example, marks of active gene promoters, which suggests that gain of DNA methylation observed in these nevus types plays a role in gene regulation.

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