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Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients

PURPOSE: Helicobacter pylori infection induces phenotype-stabilizing methylation and promotes gastric mucosal atrophy that can inhibit CpG-island methylation. Relationship between the progression of gastric mucosal atrophy and the initiation of CpG-island methylation was analyzed to delineate epigen...

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Autores principales: Oh, Jung-Hwan, Rhyu, Mun-Gan, Kim, Suk-Il, Yun, Mi-Ri, Shin, Jung-Ha, Hong, Seung-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Cancer Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334004/
https://www.ncbi.nlm.nih.gov/pubmed/29747491
http://dx.doi.org/10.4143/crt.2018.085
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author Oh, Jung-Hwan
Rhyu, Mun-Gan
Kim, Suk-Il
Yun, Mi-Ri
Shin, Jung-Ha
Hong, Seung-Jin
author_facet Oh, Jung-Hwan
Rhyu, Mun-Gan
Kim, Suk-Il
Yun, Mi-Ri
Shin, Jung-Ha
Hong, Seung-Jin
author_sort Oh, Jung-Hwan
collection PubMed
description PURPOSE: Helicobacter pylori infection induces phenotype-stabilizing methylation and promotes gastric mucosal atrophy that can inhibit CpG-island methylation. Relationship between the progression of gastric mucosal atrophy and the initiation of CpG-island methylation was analyzed to delineate epigenetic period for neoplastic transformation. MATERIALS AND METHODS: Normal-appearing gastric mucosa was biopsied from 110 H. pylori–positive controls, 95 H. pylori–negative controls, 99 gastric cancer patients, and 118 gastric dysplasia patients. Gastric atrophy was assessed using endoscopic-atrophic-border score. Methylation-variable sites of eight CpG-island genes adjacent to Alu (CDH1, ARRDC4, PPARG, and TRAPPC2L) or LTR (MMP2, CDKN2A, RUNX2, and RUNX3) retroelements and stomach-specific TFF3 gene were analyzed using radioisotope-labeled methylation-specific polymerase chain reaction. RESULTS: Mean ages of H. pylori–positive controls with mild, moderate, and severe atrophy were 51, 54, and 65 years and those of H. pylori–associated TFF3 overmethylation at the three atrophic levels (51, 58, and 63 years) tended to be periodic. Alu-adjacent overmethylation (50 years) was earlier than TFF3 overmethylation (58 years) in H. pylori–positive controls with moderate atrophy. Cancer patients with moderate atrophy showed late Alu-adjacent (58 years) overmethylation and frequent LTR-adjacent overmethylation. LTR-adjacent overmethylation was frequent in cancer (66 years) and dysplasia (68 years) patients with severe atrophy. CONCLUSION: Atrophic progression is associated with gastric cancer at moderate level by impeding the initiation of Alu-adjacent methylation. LTR-adjacent methylation is increased in cancer patients and subsequently in dysplasia patients.
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spelling pubmed-63340042019-01-22 Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients Oh, Jung-Hwan Rhyu, Mun-Gan Kim, Suk-Il Yun, Mi-Ri Shin, Jung-Ha Hong, Seung-Jin Cancer Res Treat Original Article PURPOSE: Helicobacter pylori infection induces phenotype-stabilizing methylation and promotes gastric mucosal atrophy that can inhibit CpG-island methylation. Relationship between the progression of gastric mucosal atrophy and the initiation of CpG-island methylation was analyzed to delineate epigenetic period for neoplastic transformation. MATERIALS AND METHODS: Normal-appearing gastric mucosa was biopsied from 110 H. pylori–positive controls, 95 H. pylori–negative controls, 99 gastric cancer patients, and 118 gastric dysplasia patients. Gastric atrophy was assessed using endoscopic-atrophic-border score. Methylation-variable sites of eight CpG-island genes adjacent to Alu (CDH1, ARRDC4, PPARG, and TRAPPC2L) or LTR (MMP2, CDKN2A, RUNX2, and RUNX3) retroelements and stomach-specific TFF3 gene were analyzed using radioisotope-labeled methylation-specific polymerase chain reaction. RESULTS: Mean ages of H. pylori–positive controls with mild, moderate, and severe atrophy were 51, 54, and 65 years and those of H. pylori–associated TFF3 overmethylation at the three atrophic levels (51, 58, and 63 years) tended to be periodic. Alu-adjacent overmethylation (50 years) was earlier than TFF3 overmethylation (58 years) in H. pylori–positive controls with moderate atrophy. Cancer patients with moderate atrophy showed late Alu-adjacent (58 years) overmethylation and frequent LTR-adjacent overmethylation. LTR-adjacent overmethylation was frequent in cancer (66 years) and dysplasia (68 years) patients with severe atrophy. CONCLUSION: Atrophic progression is associated with gastric cancer at moderate level by impeding the initiation of Alu-adjacent methylation. LTR-adjacent methylation is increased in cancer patients and subsequently in dysplasia patients. Korean Cancer Association 2019-01 2018-04-30 /pmc/articles/PMC6334004/ /pubmed/29747491 http://dx.doi.org/10.4143/crt.2018.085 Text en Copyright © 2019 by the Korean Cancer Association This is an Open Access article 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.
spellingShingle Original Article
Oh, Jung-Hwan
Rhyu, Mun-Gan
Kim, Suk-Il
Yun, Mi-Ri
Shin, Jung-Ha
Hong, Seung-Jin
Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients
title Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients
title_full Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients
title_fullStr Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients
title_full_unstemmed Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients
title_short Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients
title_sort gastric mucosal atrophy impedes housekeeping gene methylation in gastric cancer patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334004/
https://www.ncbi.nlm.nih.gov/pubmed/29747491
http://dx.doi.org/10.4143/crt.2018.085
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