Periodic Methylation Patterns in the Background Mucosa of Gastric Cancer
Korean J Helicobacter Up Gastrointest Res 2019;19(1):48-55
Published online March 10, 2019
© 2019 Korean College of Helicobacter and Upper Gastrointestinal Research.

Sang-Woong Kim1,*, Jung-Hwan Oh2,*, Tae Ho Kim2, Joon-Sung Kim2, Seung-Jin Hong1

Departments of Microbiology1 and Internal Medicine2, College of Medicine, The Catholic University of Korea, Seoul, Korea
Correspondence to: Seung-Jin Hong
Department of Microbiology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
Tel: +82-2-2258-7344, Fax: +82-2-596-8969, E-mail: hongsjin@catholic.ac.kr
*These authors contributed equally to this work.
Received November 19, 2018; Revised November 23, 2018; Accepted November 26, 2018.
The Korean Journal of Helicobacter and Upper Gastrointestinal Research is an Open-Access Journal. All articles are distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims: Gastrointestinal glandular stem cells renew every 8 years. New stem cells with impeded housekeeping gene methylation have unstable phenotypes and are prone to transform into malignant cells. Age-related changes in methylation in the gastric mucosa were evaluated to define the period of cancer-prone stem cell replacement.
Materials and Methods: Endoscopic biopsy specimens of normal-appearing gastric mucosa were obtained from 148 Helicobacter pylori-negative controls, 124 H. pylori-positive controls, and 69 gastric cancer patients with closed-type mucosal atrophy. Methylation-variable sites of two stomach-specific genes (TFF2 and TFF3) and four housekeeping genes (CDH1, ARRDC4, MMP2, and CDKN2A) were analyzed using radioisotope-labeled methylation-specific polymerase chain reaction. Age-related methylation was evaluated depending on the gastric mucosal atrophy at 2-year intervals.
Results: TFF2 methylation peaked periodically at 40 to 41, 48 to 49, 56 to 57, and 64 to 65 years of age in H. pylori-negative controls. Periodic peaks of TFF2 methylation were also found in H. pylori-positive controls. Housekeeping-gene methylation troughed at 48 to 49, 56 to 57, and 68 to 69 years of age in cancer patients. Trough methylation of CDH1 and ARRDC4 was lower in cancer patients than in H. pylori-positive controls.
Conclusions: Methylation peaks of stomach-specific TFF2 in controls and methylation troughs of housekeeping genes in cancer patients were found every 8 years. Periodic methylation patterns may be used to identify individuals at high risk for gastric cancer.
Keywords : Adult stem cells; DNA methylation; Gastric cancer


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