A novel reannotation strategy for dissecting DNA methylation patterns of human long intergenic non-coding RNAs in cancers.

Despite growing consensus that long intergenic non-coding ribonucleic acids (lincRNAs) are modulators of cancer, the knowledge about the deoxyribonucleic acid (DNA) methylation patterns of lincRNAs in cancers remains limited. In this study, we constructed DNA methylation profiles for 4629 tumors and 705 normal tissue samples from 20 different types of human cancer by reannotating data of DNA methylation arrays. We found that lincRNAs had different promoter methylation patterns in cancers. We classified 2461 lincRNAs into two categories and three subcategories, according to their promoter methylation patterns in tumors. LincRNAs with resistant methylation patterns in tumors had conserved transcriptional regulation regions and were ubiquitously expressed across normal tissues. By integrating cancer subtype data and patient clinical information, we identified lincRNAs with promoter methylation patterns that were associated with cancer status, subtype or prognosis for several cancers. Network analysis of aberrantly methylated lincRNAs in cancers showed that lincRNAs with aberrant methylation patterns might be involved in cancer development and progression. The methylated and demethylated lincRNAs identified in this study provide novel insights for developing cancer biomarkers and potential therapeutic targets.