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Mechanisms inactivating the gene for E-cadherin in sporadic gastric carcinomas
- Source :
- World Journal of Gastroenterology. 12:2168
- Publication Year :
- 2006
- Publisher :
- Baishideng Publishing Group Inc., 2006.
-
Abstract
- 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.
- Subjects :
- Adult
Male
Bisulfite sequencing
Loss of Heterozygosity
CDH1
Loss of heterozygosity
Germline mutation
Stomach Neoplasms
Humans
Promoter Regions, Genetic
Gene
Aged
Aged, 80 and over
Polymorphism, Genetic
biology
Cadherin
Gastroenterology
General Medicine
DNA Methylation
Middle Aged
Cadherins
Molecular biology
Gastric Cancer
Mutation
DNA methylation
biology.protein
Female
Restriction fragment length polymorphism
Subjects
Details
- ISSN :
- 10079327
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- World Journal of Gastroenterology
- Accession number :
- edsair.doi.dedup.....2b2319bc4ada41d226845fce7323683c