Inactivation of COX-2, HMLH1 and CDKN2A Gene by Promoter Methylation in Gastric Cancer: Relationship with Histological Subtype, Tumor Location and Helicobacter pylori Genotype

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorSantos Alves, Markenia Kelia
dc.creatorFerrasi, Adriana Camargo
dc.creatorLima, Valeska Portela
dc.creatorPitombeira Ferreira, Marcia Valeria
dc.creatorPardini, Maria Ines de Moura Campos
dc.creatorBarem Rabenhorst, Silvia Helena
dc.date2014-05-20T15:31:51Z
dc.date2016-10-25T18:07:51Z
dc.date2014-05-20T15:31:51Z
dc.date2016-10-25T18:07:51Z
dc.date2011-01-01
dc.date.accessioned2017-04-06T00:24:27Z
dc.date.available2017-04-06T00:24:27Z
dc.identifierPathobiology. Basel: Karger, v. 78, n. 5, p. 266-276, 2011.
dc.identifier1015-2008
dc.identifierhttp://hdl.handle.net/11449/40887
dc.identifierhttp://acervodigital.unesp.br/handle/11449/40887
dc.identifier10.1159/000329475
dc.identifierWOS:000294051600004
dc.identifierhttp://dx.doi.org/10.1159/000329475
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/883625
dc.descriptionObjective: We aimed to evaluate the inactivation of COX-2, HMLH1 and CDKN2A by promoter methylation and its relationship with the infection by different Helicobacter pylori strains in gastric cancer. Methods: DNA extracted from 76 H. pylori-positive gastric tumor samples was available for promoter methylation identification by methylation-specific PCR and H. pylori subtyping by PCR. Immunohistochemistry was used to determine COX-2, p16(INK4A) and HMLH1 expression. Results: A strong negative correlation was found between the expression of these markers and the presence of promoter methylation in their genes. Among cardia tumors, negativity of p16(INK4A) was a significant finding. on the other hand, in noncardia tumors, the histological subtypes had different gene expression patterns. In the intestinal subtype, a significant finding was HMLH1 inactivation by methylation, while in the diffuse subtype, CDKN2A inactivation by methylation was the significant finding. Tumors with methylated COX-2 and HMLH1 genes were associated with H. pylori vac A s1 (p = 0.025 and 0.047, respectively), and the nonmethylated tumors were associated with the presence of the gene flaA. Conclusions: These data suggest that the inactivation of these genes by methylation occurs by distinct pathways according to the histological subtype and tumor location and depends on the H. pylori genotype. Copyright (C) 2011 S. Karger AG, Basel
dc.languageeng
dc.publisherKarger
dc.relationPathobiology
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectGastric cancer
dc.subjectHistological subtypes
dc.subjectTumor location
dc.subjectMethylation
dc.subjectp16 (INK4A)
dc.subjectHMLH1
dc.subjectCOX-2
dc.subjectHelicobacter pylori genotypes
dc.titleInactivation of COX-2, HMLH1 and CDKN2A Gene by Promoter Methylation in Gastric Cancer: Relationship with Histological Subtype, Tumor Location and Helicobacter pylori Genotype
dc.typeOtro


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