70d4a981791bd256273aa82324d7e14d pmc_34199386.pdf d0d4a1308f241ed57f2a4656600470b294f0e3b1 pmc_34199386.pdf 5bf98866b0baba6d91625fe865d6ff955db352b8243a98b8dd7848c641f4fa9c pmc_34199386.pdf Title: Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions Subject: To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature. Keywords: precursor lesions; intestinal type of gastric cancer; CpG methylation; Helicobacter pylori; cancer risk prediction Author: Antonio Gómez, Miguel L. Pato, Luis Bujanda, Núria Sala, Osmel Companioni, Ángel Cosme, Martina Tufano, David J. Hanly, Nadia García, José Miguel Sanz-Anquela, Javier P. Gisbert, Consuelo López, José Ignacio Elizalde, Miriam Cuatrecasas, Victoria Andreu, María José Paules, María Dolores Martín-Arranz, Luis Ortega, Elvira Poves, Jesús Barrio, María Ángeles Torres, Guillermo Muñoz, Ángel Ferrández, María José Ramírez-Lázaro, Sergio Lario, Carlos A González, Manel Esteller and María Berdasco Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jun 2 10:46:31 2021 CEST ModDate: Wed Jun 2 11:08:57 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2474357 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GAJMJS+VnURWPalladioL Type 1 Custom yes yes no 10 0 QMGYAX+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 LBGXQW+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 TITEHJ+URWPalladioL-Roma Type 1 Custom yes yes 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Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Patients and Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Cell Line Culture, Demethylation Treatments and Gene Expression Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Helicobacter Pylori Infection and Genotyping Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: DNA Extraction, Bisulfite Modification and INFINIUM 450K Methylation Array Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Hierarchical Cluster Analysis and Definition of CpG Methylation Differences Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Gene Ontology Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Methylation-Site Promoter (MSP) of Candidate Genes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Children: Item: Title: Sequence-Specific CpG Methylation Reprogramming in the Intestinal Type of Gastric Cancer Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Methylation Levels in Gastric Mucosae during the Precursor Lesion Cascade and Its Dependence on Helicobacter Pylori Infection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Identification of Aberrant Promoter Methylation at RPRM and ZNF793 Genes in the Intestinal Type of Gastric Cancer Previously Established in Intestinal Metaplasia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Info: Title: Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions Author: Antonio Gómez, Miguel L. Pato, Luis Bujanda, Núria Sala, Osmel Companioni, Ángel Cosme, Martina Tufano, David J. Hanly, Nadia García, José Miguel Sanz-Anquela, Javier P. Gisbert, Consuelo López, José Ignacio Elizalde, Miriam Cuatrecasas, Victoria Andreu, María José Paules, María Dolores Martín-Arranz, Luis Ortega, Elvira Poves, Jesús Barrio, María Ángeles Torres, Guillermo Muñoz, Ángel Ferrández, María José Ramírez-Lázaro, Sergio Lario, Carlos A González, Manel Esteller and María Berdasco Subject: To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature. 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