Abstract: Abstract：0bjective To detect the expression of CDH1, screen the germ-line mutation of CDH1 exons and evaluate CDH1 promoter methylation status in a family with hereditary diffuse gastric cancer(HDGC) in China．Methods Fifteen members of a family with HDGC were visited, peripheral blood samples and tumor specimens were collected. The expression of CDH1 gene was detected by　Immunohistochemistry and Western blot. By PCR and direct sequencing germ-line mutation of 16 CDH1 exons were screened. PCR and Clone Sequencing were used to investigate the status of CDH1 promoter methylation. Results In proband and another gastric cancer patient(number 2 member), the protein expression of CDH1 were reduced in mucosa near the tumor, and lost in the tumor. In 11 members(including proband), a single nucleotide substitution of C?T (SNP) in exon 14(mRNA 2377 locus) was found. No germ-line mutation of 16 exons was detected in all members. Compare with normal mucosa, hypermethylation was found in the tumor and mucosa near the tumor of proband and number 2 member. Conclusions In this family with HDGC, abnormal expression of CDH1 may be a cause of gastric cancer. But germ-line mutation of 16 exons was not the cause of CDH1 gene inactivation in the tumor, CDH1 promoter hypermethylation may be one of reasons inducing inactivation of the gene.

Key words: Key words：hereditary diffuse gastric cancer , CDH1, promoter methylation