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Analysis of the methylation patterns of the p16 INK4A, p15 INK4B, and APC genes in gastric adenocarcinoma patients from a Brazilian population

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Tumor Biology

Abstract

Gastric cancer is a major public health problem in Pará state, where studies suggest complex genetic and epigenetic profiles of the population, indicating the need for the identification of molecular markers for this tumor type. In the present study, the methylation patterns of three genes [p16 INK4A, p15 INK4B, and adenomatous polyposis coli (APC)] were assessed in patients with gastric adenocarcinoma from Pará state in order to identify possible molecular markers of gastric carcinogenesis. DNA samples from tumoral and non-tumoral gastric tissues were modified with sodium bisulfite. A fragment of the promoter region of each gene was amplified and sequenced, and samples with more than 20 % of methylated CpG sites were considered hypermethylated. The correlation between the methylation pattern of the selected genes and the MTHFR C677T polymorphism, as well as the relationship between APC and CDH1 methylation, were evaluated. The results suggest that APC hypermethylation is an age-specific marker of gastric carcinogenesis, and the concordance of this event with CDH1 hypermethylation suggests that the Wnt pathway has an important role in gastric carcinogenesis. While the hypermethylation pattern of p15 INK4B seems to be an earlier event in this type of tumor, the hypomethylated status of this gene seems to be correlated to the C677T MTHFR TT genotype. On the other hand, the observed pattern of p16 INK4A hypermethylation suggests that this event is a good marker for the gastric cancer pathway in the Pará state population.

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Acknowledgments

The authors would like to thank the patients and hospitals who took part in this research. This research was supported by a doctoral fellowship to B.N. Borges and a research fellowship to R.R. Burbano (302774/2009-2) provided by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and by research funds from Fundação de Amparo à Pesquisa do Estado do Pará (FAPESPA).

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Authors and Affiliations

  1. Instituto Socioambiental e dos Recursos Hídricos (ISARH), Universidade Federal Rural da Amazônia, Avenida Presidente Tancredo Neves, 2501, Montese, 66077901, Belém, Pará, Brazil

    Bárbara do Nascimento Borges

  2. Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brazil

    Rommel Mario Rodriguez Burbano

  3. Laboratório de Biologia Molecular Francisco Mauro Salzano, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brazil

    Maria Lúcia Harada

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  1. Bárbara do Nascimento Borges
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  2. Rommel Mario Rodriguez Burbano
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Correspondence to Bárbara do Nascimento Borges.

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do Nascimento Borges, B., Burbano, R.M.R. & Harada, M.L. Analysis of the methylation patterns of the p16 INK4A, p15 INK4B, and APC genes in gastric adenocarcinoma patients from a Brazilian population. Tumor Biol. 34, 2127–2133 (2013). https://doi.org/10.1007/s13277-013-0742-y

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