title: Analysis of the methylation patterns of the p16 INK4A, p15 INK4B, and APC genes in gastric adenocarcinoma patients from a Brazilian population.
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.
authors.affiliation: Instituto Socioambiental e dos Recursos Hídricos (ISARH), Universidade Federal Rural da Amazônia, Avenida Presidente Tancredo Neves, 2501, Montese, 66077901, Belém, Pará, Brazil. pithecia@gmail.com
authors.forename: Bárbara
authors.initials: B
authors.lastname: do Nascimento Borges
authors.forename: Rommel Mario Rodriguez
authors.initials: RM
authors.lastname: Burbano
authors.forename: Maria Lúcia
authors.initials: ML
authors.lastname: Harada
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000235:genetics; D001938:Brazil; D015820:Cadherins / Q000235:genetics; D018899:CpG Islands; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D019942:Genes, p16; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D004273:DNA, Neoplasm; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)