BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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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)
  • 투고 : 2023.06.12
  • 심사 : 2023.08.14
  • 발행 : 2023.10.31
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초록

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.

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과제정보

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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