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Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers
Sejoon Lee1 (Professor), Kil-yong Lee 2 (Medical Doctor), Ji-Hwan Park 3,4 (Research Worker), Jin-Young Lee 6,* (Research Worker), Young-Joon Kim 6 (Professor), Jin Ok Yang 1 (Research Worker), Jaeim Lee 2 (Medical Doctor), Sung-Bum Kang 5 (Medical Doctor)
1Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea,
2Department of Surgery, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu 11765, Republic of Korea,
3Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea,
4Department of Bioscience, University of Science and Technology (UST), Daejeon 34113, Republic of Korea,
5Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea,
6Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
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. A variety of CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, those markers have not been validated for Korean patients because of the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles of 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array, and 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, whereas hypomethylated positions were enriched in open-sea regions that are considerably distant from CpG islands. After applying a CpG island methylator phenotype 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 and showed a higher prevalence of microsatellite instability status and MLH1 methylation than the tumors with low or non-CIMP signatures. Therefore, our methylome analysis and dataset can provide insights into the application of the CRC-associated methylation markers for Korean patients, regarding cancer diagnosis and prognosis.
Abstract, Accepted Manuscript(in press) [Submitted on June 19, 2023, Accepted on November 13, 2023]
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