Dataset Information

DNA Methylation Predicts Progression of Human Gastric Lesions.

ABSTRACT: Development of the intestinal subtype of gastric adenocarcinoma is marked by a progression of histopathologic lesions. Residents of the Andean regions of Colombia are at high risk for gastric cancer.A cohort of 976 Colombian subjects was followed over 16 years examining effects of Helicobacter pylori eradication and treatment with antioxidants on progression of lesions. We performed methylation analysis of DNA from baseline antral biopsies from 104 subjects for whom follow-up data were available for at least 12 years. Methylation was quantitated for AMPH, CDKN2A, CDH1, EN1, EMX1, NKX6-1, PCDH10, RPRM, RSPO2, SORCS3, ZIC1, and ZNF610 genes, using Pyrosequencing.Levels of DNA methylation were associated with baseline diagnosis for AMPH, EMX1, RPRM, RSPO2, SORCS3, and ZNF610. After adjusting for baseline diagnosis and H. pylori infection, methylation levels of AMPH, PCDH10, RSPO2, and ZNF610 had progression coefficients that increased and P values that decreased over 6, 12, and 16 years. Methylation for SORCS3 was associated with progression at all 3 time points but without the continual strengthening of the effect. Scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes were unrelated to progression.Methylation levels of AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 predict progression of gastric lesions independent of the effect of duration of H. pylori infection, baseline diagnosis, gender of the patient, or scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes.DNA methylation levels in AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 may contribute to identification of persons with gastric lesions likely to progress.

SUBMITTER: Schneider BG

PROVIDER: S-EPMC4592454 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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DNA Methylation Predicts Progression of Human Gastric Lesions.

Schneider Barbara G BG Mera Robertino R Piazuelo M Blanca MB Bravo Juan C JC Zabaleta Jovanny J Delgado Alberto G AG Bravo Luis E LE Wilson Keith T KT El-Rifai Wael W Peek Richard M RM Correa Pelayo P

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20150812 10

<h4>Background</h4>Development of the intestinal subtype of gastric adenocarcinoma is marked by a progression of histopathologic lesions. Residents of the Andean regions of Colombia are at high risk for gastric cancer.<h4>Methods</h4>A cohort of 976 Colombian subjects was followed over 16 years examining effects of Helicobacter pylori eradication and treatment with antioxidants on progression of lesions. We performed methylation analysis of DNA from baseline antral biopsies from 104 subjects for ...[more]

PMID: 26269563

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Project description:Epigenetic inactivation of genes by DNA hypermethylation plays an important role in carcinogenesis. An in vitro model of human breast epithelial cell transformation was used to study epigenetic changes induced by estradiol during the neoplastic process. Different stages of tumor initiation and progression are represented in this model being MCF-10F the normal stage; trMCF cells, the transformed stage; bsMCF cells, the invasive stage and, caMCF cells, the tumor stage. Global methylation studies by restriction landmark genomic scanning (RLGS) showed an increased DNA methylation during the in the invasive and tumor stages. Expression studies showed that NRG1 (neuregulin 1), CSS3 (chondroitin sulfate synthase 3) and SNIP (SNAP-25-interacting protein) were downregulated in the invasive and tumor cells. The transformed cells showed low expression of STXBP6 (amysin) compared to the parental cells MCF-10F. The treatment of these cells with the demethylating agent 5-aza-dC alone or in combination with the histone deacetylase inhibitor trichostatin increased the expression of NRG1, STXBP6, CSS3 and SNIP confirming that DNA methylation plays an important role in the regulation of the expression of these genes. The NRG1 exon 1 has a region located between -136 and +79 (considering +1, the translational initiation site) rich in CpG sites that was analyzed by methylation specific PCR (MSP). NRG1 exon 1 showed progressive changes in the methylation pattern associated with the progression of the neoplastic process in this model; NRG1 exon 1 was unmethylated in MCF-10F and trMCF cells, becoming hypermethylated in the invasive (bsMCF) and tumor (caMCF) stages. Studies of human breast tissue samples showed that NRG1 exon 1 was partially methylated in 14 out of 17 (82.4%) invasive carcinomas although it was unmethylated in normal tissues (8 out of 10 normal breast tissue samples). Furthermore, NRG1 exon 1 was partially methylated in 9 out of 14 (64.3%) morphologically normal tissue samples adjacent to invasive carcinomas.

Dataset Information

DNA Methylation Predicts Progression of Human Gastric Lesions.

Publications

DNA Methylation Predicts Progression of Human Gastric Lesions.

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