Alterations in the LINE-1 methylation pattern in patients with lichen simplex chronicus.

BACKGROUND Long interspersed element-1 (LINE-1) and short interspersed element (Alu) retrotransposons have been identified to influence the human genome by modifications in gene expression. Variations in LINE-1 and Alu methylation have been shown to be associated with many diseases, predominantly malignancies and autoimmune diseases. Moreover, the degree and pattern of LINE-1 methylation are related to risk, prognosis and aggressiveness of several cancers. However, a similar study has not been performed in lichen simplex chronicus (LSC). OBJECTIVE To evaluate DNA methylation status of repetitive sequences in LSC. RESULTS The %mCmC of LINE-1 was significantly decreased in keratinocytes from patients with LSC (p=0.012). Moreover, the %mCuC was significantly lower in LSC than controls (p=0.029). Conversely, %uCmC was significantly higher LSC than controls (p=0.004). A receiver-operating characteristic (ROC) curve analysis demonstrated that % mCmC, % mCuC and % uCmC were highly sensitive and specific for LSC with an optimal cut-off value. There were no significant differences in Alu methylation in keratinocytes from LSC patients. METHODS We determined the level and pattern of LINE-1 and Alu methylation in keratinocytes from patients with LSC (n=10) compared to normal controls (n=13), by the improved combined bisulfite restriction analysis of LINE-1 and Alu (COBRA-LINE-1 and Alu). COBRA-LINE-1 classifies LINE-1 loci according to the methylation patterns of two CpG dinucleotides in the 5'UTR into four categories: hypermethylated (mCmC), hypomethylated (uCuC), and two forms of partially methylated loci (uCmC and mCuC). CONCLUSION Changes in the LINE-1 pattern were revealed in the epidermis from patients with LSC. A particular LINE-1 methylation pattern is indicative of LSC and might be used as a diagnostic tool.