Genome-scale DNA methylation analysis identifies repeat element alterations that modulate the genomic stability of melanocytic nevi
2021
ABSTRACT Acquired melanocytic nevi grow and persist in a stable form into adulthood. Using genome-wide methylation profiling, we evaluated 32 histopathologically and dermoscopically characterized nevi, to identify key epigenetic regulatory mechanisms involved in nevogenesis. Benign (69% globular and 31% non-specific dermoscopic pattern) and dysplastic (95% reticular/nonspecific dermoscopic pattern) nevi were dissimilar with only two shared differentially methylated (DM) loci. 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 (Alu; P=0.00019 and LINE-1; P=0.000035). Using dermoscopic classifications, reticular/non-specific patterned nevi had 59,572 CpG DM loci (Q
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