Epigenetic insights into colorectal cancer: comprehensive genome-wide DNA methylation profiling of 294 patients in Korea
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DNA methylation regulates gene expression and contributes totumorigenesis in the early stages of cancer. In colorectal cancer(CRC), CpG island methylator phenotype (CIMP) is recognizedas a distinct subset that is associated with specific molecularand clinical features. In this study, we investigated the genomewideDNA methylation patterns among patients with CRC. The methylation data of 1 unmatched normal, 142 adjacentnormal, and 294 tumor samples were analyzed. We identified40,003 differentially methylated positions with 6,933 (79.8%)hypermethylated and 16,145 (51.6%) hypomethylated probesin the genic region. Hypermethylated probes were predominantlyfound in promoter-like regions, CpG islands, and N shore sites;hypomethylated probes were enriched in open-sea regions. CRC tumors were categorized into three CIMP subgroups, with90 (30.6%) in the CIMP-high (CIMP-H), 115 (39.1%) in theCIMP-low (CIMP-L), and 89 (30.3%) in the non-CIMP group. The CIMP-H group was associated with microsatellite instabilityhightumors, hypermethylation of MLH1, older age, and rightsidedtumors. Our results showed that genome-wide methylationanalyses classified patients with CRC into three subgroupsaccording to CIMP levels, with clinical and molecular featuresconsistent with previous data.
Abstract
DNA methylation regulates gene expression and contributes totumorigenesis in the early stages of cancer. In colorectal cancer(CRC), CpG island methylator phenotype (CIMP) is recognizedas a distinct subset that is associated with specific molecularand clinical features. In this study, we investigated the genomewideDNA methylation patterns among patients with CRC. The methylation data of 1 unmatched normal, 142 adjacentnormal, and 294 tumor samples were analyzed. We identified40,003 differentially methylated positions with 6,933 (79.8%)hypermethylated and 16,145 (51.6%) hypomethylated probesin the genic region. Hypermethylated probes were predominantlyfound in promoter-like regions, CpG islands, and N shore sites;hypomethylated probes were enriched in open-sea regions. CRC tumors were categorized into three CIMP subgroups, with90 (30.6%) in the CIMP-high (CIMP-H), 115 (39.1%) in theCIMP-low (CIMP-L), and 89 (30.3%) in the non-CIMP group. The CIMP-H group was associated with microsatellite instabilityhightumors, hypermethylation of MLH1, older age, and rightsidedtumors. Our results showed that genome-wide methylationanalyses classified patients with CRC into three subgroupsaccording to CIMP levels, with clinical and molecular featuresconsistent with previous data.
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