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Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer

  • Hyeran Shim (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Kiwon Jang (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Yeong Hak Bang (Department of Digital Health, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan 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) ;
  • Jin-Young Lee (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Sheehyun Cho (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) ;
  • Jongbum Jeon (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Taeyeon Hwang (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Soobok Joe (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Jinyeong Lim (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University) ;
  • Ji-Hye Choi (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University) ;
  • Eun Hye Joo (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University) ;
  • Kyunghee Park (Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Ji Hwan Moon (Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kyung Yeon Han (Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Yourae Hong (Department of Oncology, Katholieke Universiteit Leuven) ;
  • Woo Yong Lee (Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Hee Cheol Kim (Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Seong Hyeon Yun (Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Yong Beom Cho (Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Yoon Ah Park (Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jung Wook Huh (Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jung Kyong Shin (Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Dae Hee Pyo (Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Hyekyung Hong (Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Hae-Ock Lee (Department of Microbiology, College of Medicine, The Catholic University of Korea) ;
  • Woong-Yang Park (Department of Digital Health, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University) ;
  • Jin Ok Yang (Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology) ;
  • Young-Joon Kim (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University)
  • Received : 2023.06.02
  • Accepted : 2023.08.21
  • Published : 2024.02.29

Abstract

Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions. The CpG Island Methylator Phenotype-High (CIMP-H) exhibited notable enrichment of microsatellite instability-high (MSI-H). Additionally, our findings indicated a significant correlation between methylation of the MLH1 gene and MSI-H status. Furthermore, we found that the CIMP-H had a higher tendency to affect the right-side of the colon tissues and was slightly more prevalent among older patients. Through our methylome profile analysis, we successfully verified the methylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundation for exploring novel molecular insights and potential therapeutic targets for the treatment of CRC.

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, NRF-2017M3A9A7050803, and NRF-2017M3A9A7050610). It was additionally supported by a grant from the National Research Foundation of Korea (NRF-2020M3A9I6A01036057).

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