E-Cadherin Gene Promoter Hypermethylation in Primary Human Gastric Carcinomas
Journal of the National Cancer Institute. (2000) 92 (7): 569-573
By Tamura, Gen et al.
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E (epithelial)-cadherin is a cell adhesion molecule that is believed to be a tumor metastasis/invasion suppressor. E-cadherin is mutationally inactivated in nearly half of diffuse type gastric carcinomas. Epigenetic silencing via CpG methylation at the promoter region of E-cadherin has also been reported in several cases. In this study, CpG methylation status of the E-cadherin promoter was examined in 53 primary human gastric carcinomas. Hypermethylation of the promoter region was observed in 51% of the gastric carcinomas examined. This hypermethylation was more frequent in diffuse type gastric carcinomas (83%), reinforcing the role of CDH1 in this specific type of gastric cancer. Sequencing of the promoter regions found complete methylation of CpG regions in silenced alleles and no methylation of CpG regions in wild type alleles. Methylation status was predictive of E-cadherin status in 83% of tumor tissues. That is, hypermethylation resulted in silencing of E-cadherin expression in tumors, and absence of methylation resulted in normal expression of E-cadherin in tumors. This study reinforced the role of E-cadherin inactivation in the majority of diffuse type gastric carcinomas. E-cadherin can be inactivated by genetic (usually point mutation) and epigenetic (hypermethylation) mechanisms. These results indicate that CDH1 is one of the most definitive and common tumor suppressor genes identified in human stomach cancer thus far.
For pdf of full text, click HERE
E (epithelial)-cadherin is a cell adhesion molecule that is believed to be a tumor metastasis/invasion suppressor. E-cadherin is mutationally inactivated in nearly half of diffuse type gastric carcinomas. Epigenetic silencing via CpG methylation at the promoter region of E-cadherin has also been reported in several cases. In this study, CpG methylation status of the E-cadherin promoter was examined in 53 primary human gastric carcinomas. Hypermethylation of the promoter region was observed in 51% of the gastric carcinomas examined. This hypermethylation was more frequent in diffuse type gastric carcinomas (83%), reinforcing the role of CDH1 in this specific type of gastric cancer. Sequencing of the promoter regions found complete methylation of CpG regions in silenced alleles and no methylation of CpG regions in wild type alleles. Methylation status was predictive of E-cadherin status in 83% of tumor tissues. That is, hypermethylation resulted in silencing of E-cadherin expression in tumors, and absence of methylation resulted in normal expression of E-cadherin in tumors. This study reinforced the role of E-cadherin inactivation in the majority of diffuse type gastric carcinomas. E-cadherin can be inactivated by genetic (usually point mutation) and epigenetic (hypermethylation) mechanisms. These results indicate that CDH1 is one of the most definitive and common tumor suppressor genes identified in human stomach cancer thus far.