E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma

• Tipo: Artigo em Revista Científica Internacional
• Data: 2001

Autores

Machado, JC (Autor) FMUP; Oliveira, C (Autor) Outra; Carvalho, R (Autor) Outra; Soares, P (Autor) FMUP; Berx, G (Autor) Outra; Caldas, C (Autor) Outra; Seruca, R (Autor) FMUP; Carneiro, F (Autor) FMUP; Sobrinho Simoes, M (Autor) FMUP

Revista

Título: Oncogene

Vol. 20

Páginas: 1525-1528

ISSN: 0950-9232

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 224 Citações

Scopus - 262 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina clínica

Outras Informações

ID Authenticus: P-000-W2W

DOI: 10.1038/sj.onc.1204234

Abstract (EN): In diffuse gastric carcinoma, despite common E-cadherin gene (CDH1) mutations, tumors show absence of CDH1 loss of heterozigosity (LOH) in most cases. This observation challenges the classical two-hit model of tumor suppresser gene inactivation. In order to investigate whether or not CDH1 promoter methylation may function as the second hit we analysed a series of 23 sporadic gastric carcinomas for the presence of CDH1 mutations, CDH1 promoter methylation, LOH and E-cadherin expression. CDH1 mutations were detected in nine of the 16 (56.3%) diffuse gastric carcinomas and in none of the seven intestinal gastric carcinomas. In diffuse gastric carcinomas harboring CDH1 mutations, LOH was observed in a single case. Loss of plasma membrane E-cadherin expression was consistently found in all nine cases with CDH1 mutation, suggesting that tumors inactivated the remaining CDH1 allele via a different mechanism. CDH1 promoter methylation was observed in nine of the 16 (56.3%) diffuse-type gastric carcinoma cases, including six of the nine cases (66.7%) harboring CDH1 mutations. CDH1 promoter methylation was also seen in two (28.6%) intestinal-type cases. Our results show that CDH1 promoter methylation is the second hit in more than half of the sporadic diffuse gastric carcinoma cases harboring CDH1 mutations.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 4