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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Epigenetic insights into colorectal cancer: comprehensive genome-wide DNA methylation profiling of 294 patients in Korea

  • Soobok Joe (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Jinyong Kim (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Jin-Young Lee (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Jongbum Jeon (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Iksu Byeon (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Sae-Won Han (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Seung-Bum Ryoo (Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kyu Joo Park (Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Sang-Hyun Song (Cancer Research Institute, Seoul National University College of Medicine) ;
  • Sheehyun Cho (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Hyeran Shim (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Hoang Bao Khanh Chu (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Jisun Kang (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Hong Seok Lee (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • DongWoo Kim (Cellgentek) ;
  • Young-Joon Kim (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Tae-You Kim (Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Seon-Young Kim (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2023.06.12
  • Accepted : 2023.08.14
  • Published : 2023.10.31
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Abstract

DNA methylation regulates gene expression and contributes to tumorigenesis in the early stages of cancer. In colorectal cancer (CRC), CpG island methylator phenotype (CIMP) is recognized as a distinct subset that is associated with specific molecular and clinical features. In this study, we investigated the genome-wide DNA methylation patterns among patients with CRC. The methylation data of 1 unmatched normal, 142 adjacent normal, and 294 tumor samples were analyzed. We identified 40,003 differentially methylated positions with 6,933 (79.8%) hypermethylated and 16,145 (51.6%) hypomethylated probes in the genic region. Hypermethylated probes were predominantly found 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, with 90 (30.6%) in the CIMP-high (CIMP-H), 115 (39.1%) in the CIMP-low (CIMP-L), and 89 (30.3%) in the non-CIMP group. The CIMP-H group was associated with microsatellite instability-high tumors, hypermethylation of MLH1, older age, and right-sided tumors. Our results showed that genome-wide methylation analyses classified patients with CRC into three subgroups according to CIMP levels, with clinical and molecular features consistent with previous data.

Keywords

Acknowledgement

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (grant number: NRF-2017M3A9A7050614 and NRF-2017M3A9A7050610). It was additionally supported by a grant from the National Research Foundation of Korea (NRF-2020M3A9I6A01036057).

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