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

• Type: Article in International Scientific Journal
• Date: 2001

Authors

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

Journal

Title: Oncogene

Vol. 20

Pages: 1525-1528

ISSN: 0950-9232

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 224 Citations

Scopus - 262 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 4