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

被引:216
作者
Machado, JC
Oliveira, C
Carvalho, R
Soares, P
Berx, G
Caldas, C
Seruca, R
Carneiro, F
Sobrinho-Simoes, M
机构
[1] IPATIMUP, P-4200 Oporto, Portugal
[2] Univ Cambridge, Dept Oncol, Cambridge CB2 2XY, England
[3] VIB Ghent Univ, KL, Dept Mol Biol, B-9000 Ghent, Belgium
[4] Univ Porto, Fac Med, P-4200 Oporto, Portugal
关键词
E-cadherin; mutation; methylation; gastric cancer; stomach; diffuse cancer;
D O I
10.1038/sj.onc.1204234
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1525 / 1528
页数:4
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