Analysis of mutations and polymorphisms in CDH1 gene in sporadic gastric cancers
gastric cancer ; CDH1 promoter methylation ; E-cadherin
The calcium-dependent cell adhesion molecule E-cadherin is encoded by tumor suppressor gene (CDH1) located on chromosome 16q22.1. The protein plays a crucial role in cell-cell adhesion, maintaining cell polarity and the normal architecture of epithelium. E-cadherin trough catenins complex with cytoskeleton to form very tight adherens junctions. In normal tissues in embryogenesis, during cell differentiation and development process, the CpG methylation is present. Materials and methods The tumour and normal samples were obtained from 84 patients attending the Pathomorphology Department CMUJ. The search for polymorphisms and mutations in the CDH1 gene was performed using SSCP. After re-amplification all samples with new bands or bandshifts were sequenced. The methylation status of the promoter of the CDH1 gene was determined by MSP. Results 77% of all cases showed CDH1 polimorphisms. We found a novel change R732R. We detected CDH1 mutations in 15,5% (13/84) cases. By accident 3 germline changes in E-cadherin were found. We described tendency to accumulation of CDH1 sporadic mutations along the gene. In diffused gastric cancers mutations spread along exon4–intron 6, in mixed type gastric carcinomas mutations were widely spread along exons 7-14. We detected CDH1 promoter hypermethylation in 54,8% of gastric cancers. In Goseki’s classification we observed significance between Goseki ; ’s type and hipermethylation, where p=0.01. The highest percentage of methylation we found in Goseki III group (signet ring cells) (83%), and the lowest in group IV (36%).