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Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer
Hyeran Shim1 (Graduate student), Kiwon Jang 2 (Research worker), Yeong Hak Bang 3,4 (Medical Doctor), Jisun Kang 1 (Graduate student), Jin-Young Lee 1,* (Research worker), Sheehyun Cho 1 (Graduate student), Hong Seok Lee1 (Research Professor), Jongbum Jeon 2 (Research worker), Taeyeon Hwang2 (Research worker), Soobok Joe 2 (Research worker), Jinyeong Lim5 (Graduate student), Woo Yong Lee7 (Doctor), Woong-Yang Park 3,5,6 (Professor), Jin Ok Yang 2 (Research worker), Young-Joon Kim 1 (Professor)
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea,
2Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea,
3Department of Digital Health, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul 06355, Republic of Korea,
4Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea,
5Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06355, Republic of Korea,
6Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Republic of Korea,
7Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea,
8Department of Oncology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium,
9Department of Microbiology, The Catholic University of Korea, Seoul, 06591, Republic of Korea
Abstract
DNA methylation alterations play an important pathophysiological role in the development and progression of colorectal cancer. In this study, we extensively analyzed the DNA methylation patterns of 165 Korean patients diagnosed with colorectal cancer (CRC) using a comprehensive profiling approach. Our analysis revealed that the tumor samples included a multitude of hypomethylated probes and few hypermethylated probes. A larger proportion of hypermethylated probes were located in promoter-like and CpG island regions, whereas hypomethylated probes were primarily found within gene body regions. A CIMP-H group, which is one of three distinct CpG island methylator phenotypes, was also marked by a significant enrichment of microsatellite instability (MSI) status sites, especially MSI-H. Further, our data pointed to a compelling association between MLH1 methylation and MSI-H status. Furthermore, the CIMP-H group phenotype more frequently affected the right-side colon tissues and marginally older patients. Consequently. This methylome profile set is uniquely capable of correlating the clinical features of CRC in Korean patients given the paucity of existing reports on the methylome of Korean CRC patients. Despite limitations, such as the single-center design and small study population, our study successfully reflected general cancer characteristics, such as age, sex, tumor stage, and location, as outlined in other studies. We believe that the CRC methylome profile created in this study will facilitate CRC development by offering valuable insights into methylation patterns and may guide future endeavors in molecular characterization, discovery of potential biomarkers, and analysis of CRC treatment modalities.
Abstract, Accepted Manuscript(in press) [Submitted on June 2, 2023, Accepted on August 21, 2023]
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