Detailed methylation map of LINE-1 5'-promoter region reveals hypomethylated CpG hotspots associated with tumor tissue specificity.

BACKGROUND: Long interspersed nuclear elements (LINE-1) sequences constitute a substantial portion of the human genome, and their methylation often correlating with global genomic methylation. Previous studies have highlighted the feasibility of using LINE-1 methylation to discriminate tumors from healthy tissues. However, most studies are based on only a few specific LINE-1 CpG sites.

METHODS: Herein, we have performed a systematic fine-scale analysis of methylation at 14 CpGs located in the 5'-region of consensus LINE-1, in bladder, colon, prostate, and gastric tumor tissues using a global degenerate approach.

RESULTS: Our results reveal variable methylation levels between different CpGs, as well as some tissue-specific differences. Trends toward hypomethylation were observed in all tumors types to certain degrees, showing statistically significance in bladder and prostate tumors. Our data points toward the presence of unique LINE-1 DNA methylation patterns for each tumor type and tissue, indicating that not the same CpGs will be informative for testing in all tumor types.

CONCLUSION: This study provides an accurate guide that will help to design further assays that could avoid artifacts and explain the variability of obtained LINE-1 methylation values between different studies.

© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

PMID: 30955237