Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers

Abstract

Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5’ untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis.