Genome-wide open chromatin methylome profiles in colorectal cancer

The methylome of open chromatins was investigated in colorectal cancer (CRC) to explore cancer-specific methylation and potential biomarkers. Epigenome-wide methylome of open chromatins was studied in colorectal cancer tissues using Infinium DNA MethylationEPIC assay. Differentially methylated regions were identified using the ChAMP Bioconductor. Our stringent analysis led to the discovery of 2187 significant differentially methylated open chromatins in CRCs. More hypomethylated probes were observed and the trend was similar across all chromosomes. Majority of hyper- and hypomethylated probes in open chromatin were in chromosome 1. Our unsupervised hierarchical clustering analysis showed that 40 significant differentially methylated open chromatins were able to segregate CRC from normal colonic tissues. Receiver operating characteristic analyses from the top 40 probes revealed several significant, highly discriminative, specific and sensitive probes such as OPLAH cg26256223, EYA4 cg01328892, and CCNA1 cg11513637, among others. OPLAH cg26256223 hypermethylation is associated with reduced gene expression in the CRC. This study reports many open chromatin loci with novel differential methylation statuses, some of which with the potential as candidate markers for diagnostic purposes. The Infinium DNA MethylationEPIC assay was performed on 24 CRC and normal adjacent colon from 12 patients according to the manufacturer’s specifications and the beadchips were scanned using iScan (Illumina, Inc., USA). The Illumina Infinium DNA MethylationEPIC assay examines the DNA methylation status of > 850,000 CpG dinucleotides distributed over the whole genome, including > 220,000 open chromatins.