Mechanisms inactivating the gene for E-cadherin in sporadic gastric carcinomas

被引:38
作者
Liu, Yao-Chi
Shen, Chen-Yang
Wu, Hurng-Sheng
Hsieh, Tsai-Yuan
Chan, De-Chuan
Chen, Cheng-Jueng
Yu, Jyh-Cherng
Yu, Cheng-Ping
Harn, Horng-Jyh
Chen, Peng-Jen
Hsieh, Chung-Bao
Chen, Teng-Wei
Hsu, Huan-Mieng
机构
[1] Tri Serv Gen Hosp, Div Gen Surg, Dept Surg, Natl Def Med Ctr, Taipei 114, Taiwan
[2] Tri Serv Gen Hosp, Div Gastroenterol, Dept Internal Med, Natl Def Med Ctr, Taipei 114, Taiwan
[3] Tri Serv Gen Hosp, Dept Pathol, Natl Def Med Ctr, Taipei 114, Taiwan
[4] Buddhist Tzu Chi Gen Hosp, Dept Pathol, Hualien, Taiwan
[5] Show Chwan Mem Hosp, Dept Surg, Changhua, Taiwan
[6] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan
关键词
gastric carcinoma; E-cadherin gene alteration profiles; inactivation of E-cadherin;
D O I
10.3748/wjg.v12.i14.2161
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: To study the role of CDH1/E-cadherin (E-cad) gene alteration profiles including mutation, loss of heterozygosity (LOH), promoter polymorphism and hypermethylation in mechanisms of CDH1 inactivation in gastric carcinoma (GC). METHODS: Specimens were collected surgically from 70 patients with GC. Allelotyping PCR and detection of LOH, denaturing high pressure liquid chromatography and DNA sequencing, restriction fragment length polymorphism analysis, methylation specific PCR, and immunohistochemical staining were used. RESULTS: Promoter polymorphism was not a major mechanism of E-cad inactivation. Only one truncating mutation was found in a diffuse type tumor (3%). Both LOH and promoter hypermethylation were major mechanisms of E-cad inactivation, but interestingly, there was a negative association between the fraction of allelic loss (LOH) in tumors and hypermethylation of CDH1. Therefore LOH and hypermethylation were two different tumorigenic pathways involved in GC. CONCLUSION: Given the findings that somatic mutation was extremely low and the relationship between LOH and hypermethylation was inverse, any two combinations of these three factors cannot fulfill the classical two-hit hypothesis of CDH1 inactivation. Thus, other mechanisms operating at the transcriptional level or at the post-translational level might be required to induce E-cadherin inactivation. (c) 2006 The WJG Press. All rights reserved.
引用
收藏
页码:2168 / 2173
页数:6
相关论文
共 42 条
[1]   Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer [J].
Ascaño, JJ ;
Frierson, H ;
Moskaluk, CA ;
Harper, JC ;
Roviello, F ;
Jackson, CE ;
El-Rifai, W ;
Vindigni, C ;
Tosi, P ;
Powell, SM .
MODERN PATHOLOGY, 2001, 14 (10) :942-949
[2]   The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells [J].
Batlle, E ;
Sancho, E ;
Franci, C ;
Domínguez, D ;
Monfar, M ;
Baulida, J ;
de Herreros, AG .
NATURE CELL BIOLOGY, 2000, 2 (02) :84-89
[3]  
BECKER KF, 1994, CANCER RES, V54, P3845
[4]  
Berx G, 1998, HUM MUTAT, V12, P226, DOI 10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO
[5]  
2-D
[6]  
Berx G, 1996, ONCOGENE, V13, P1919
[7]  
BUSSEMAKERS MJG, 1992, CANCER RES, V52, P2916
[8]   The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression [J].
Cano, A ;
Pérez-Moreno, MA ;
Rodrigo, I ;
Locascio, A ;
Blanco, MJ ;
del Barrio, MG ;
Portillo, F ;
Nieto, MA .
NATURE CELL BIOLOGY, 2000, 2 (02) :76-83
[9]   Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer [J].
Chan, AOO ;
Lam, SK ;
Wong, BCY ;
Wong, WM ;
Yuen, MF ;
Yeung, YH ;
Hui, WM ;
Rashid, A ;
Kwong, YL .
GUT, 2003, 52 (04) :502-506
[10]   Cooccurrence of reduced expression of α-catenin and overexpression of p53 is a predictor of lymph node metastasis in early gastric cancer [J].
Che, XM ;
Hokita, S ;
Natsugoe, S ;
Tanabe, G ;
Baba, M ;
Takao, S ;
Kuroshima, K ;
Aikou, T .
ONCOLOGY, 1999, 57 (02) :131-137