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©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
Mechanisms inactivating the gene for E-cadherin in sporadic gastric carcinomas
Yao-Chi Liu, Chen-Yang Shen, Hurng-Sheng Wu, Tsai-Yuan Hsieh, De-Chuan Chan, Cheng-Jueng Chen, Jyh-Cherng Yu, Cheng-Ping Yu, Horng-Jyh Harn, Peng-Jen Chen, Chung-Bao Hsieh, Teng-Wei Chen, Huan-Mieng Hsu
Yao-Chi Liu, De-Chuan Chan, Cheng-Jueng Chen, Jyh-Cherng Yu, Chung-Bao Hsieh, Teng-Wei Chen, Huan-Mieng Hsu, Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China
Tsai-Yuan Hsieh, Peng-Jen Chen, Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China
Cheng-Ping Yu, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China
Horng-Jyh Harn, Department of Pathology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan, China
Hurng-Sheng Wu, Department of Surgery, Show Chwan Memorial Hospital, Changhua, Taiwan, China
Chen-Yang Shen, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, China
Supported by Clinical Research Fund of the Tri-Service General Hospital and C.Y.Fundation for Advancement of Education, Science and Medicine, Taipei, Taiwan, China
Correspondence to: Dr. Yao-Chi Liu, Division of General Surgery, Tri-Service General Hospital. No. 325, Sec 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, China. dlyaochi@yahoo.com.tw
Telephone: +886-2-87927191 Fax: +886-2-87927372
Received: March 29, 2005
Revised: May 1, 2005
Accepted: July 20, 2005
Published online: April 14, 2006
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.
