Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil

Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil

Author Leal, Mariana Ferreira Autor UNIFESP Google Scholar
Lima, Eleonidas Moura Google Scholar
Silva, Patricia Natalia Oliveira da Autor UNIFESP Google Scholar
Assumpcao, Paulo Pimentel Google Scholar
Calcagno, Danielle Queiroz Autor UNIFESP Google Scholar
Payão, Spencer Luiz Marques Autor UNIFESP Google Scholar
Burbano, Rommel Rodriguez Autor UNIFESP Google Scholar
Smith, Marilia de Arruda Cardoso Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Fed Piaui
Fed Univ Para
Fac Med Marilia
Abstract AIM: To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics.METHODS: Methylation-specific PCR (MSP) assay was performed in 13 nonneoplastic gastric adenocarcinoma, 30 intestinal-type gastric adenocarcinoma and 35 diffuse-type gastric adenocarcinoma samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher's exact test to assess associations between methylation status and clinicopathological characteristics.RESULTS: Hypermethylation frequencies of CDH1,, FHIT, MTAP and PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hypermethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hypermethylation frequency was significantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender.CONCLUSION: Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition. (C) 2007 The WJG Press. All rights reserved.
Keywords gastric adenocarcinoma
DNA hypermethylation
Language English
Date 2007-05-14
Published in World Journal Of Gastroenterology. Beijing: W J G Press, v. 13, n. 18, p. 2568-2574, 2007.
ISSN 1007-9327 (Sherpa/Romeo, impact factor)
Publisher W J G Press
Extent 2568-2574
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000247024700006

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