title: DNA methylation accumulation and its predetermination of future cancer phenotypes.
abstract: Aberant DNA methylation is a common epigenomic alteration in carcinogenesis. Comprehensive analyses of DNA methylation have stratified gastrointestinal cancer into several subgroups according to specific DNA methylation accumulation. In gastric cancer, Helicobacter pylori infection is a cause of methylation accumulation in apparently normal mucosa. Epstein-Barr virus infection is another methylation inducer that causes more genome-wide methylation, resulting in the formation of unique epigenotype with extensive methylation. In colorectal carcinogenesis, accumulation of high levels of methylation in combination with BRAF mutation is characteristic of the serrated pathway, but not of the adenoma-carcinoma sequence through conventional adenoma. In a de novo pathway, laterally spreading tumours generate intermediate- and low-methylation epigenotypes, accompanied by different genetic features and different macroscopic morphologies. These methylation epigenotypes, with specific genomic aberrations, are mostly completed by the adenoma stage, and additional molecular aberration, such as TP53 mutation, is suggested to lead to cancer development with the corresponding epigenotype. Accumulation of DNA methylation and formation of the epigenotype is suggested to occur during the early stages of carcinogenesis and predetermines the future cancer type.
authors: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; and Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama 236-0004, JapanDepartment of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; and Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan kaneda@chiba-u.jp.
authors: Atsushi
authors: A
authors: Kaneda
authors: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; and Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama 236-0004, JapanDepartment of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; and Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors: Keisuke
authors: K
authors: Matsusaka
authors: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; and Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama 236-0004, JapanDepartment of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; and Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors: Eiji
authors: E
authors: Sakai
authors: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; and Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama 236-0004, JapanDepartment of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; and Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors: Sayaka
authors: S
authors: Funata
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics; D019175:DNA Methylation; D020031:Epstein-Barr Virus Infections / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D059647:Gene-Environment Interaction; D016481:Helicobacter Infections / Q000235:genetics; D006801:Humans; D009857:Oncogenes; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology
keywords: CpG island methylator phenotype (CIMP); DNA methylation; colorectal cancer; epigenetics; gastric cancer