摘要目的 检测30例伴家族史胃癌和8例遗传性胃癌家系患者的E-钙黏附素基因(CDH1)的蛋白表达和启动子甲基化及胚系突变情况,探讨CDH1基因在我国家族性遗传性胃癌中的意义.方法 采用免疫组织化学、甲基化特异性PCR(MS-PCR)、变性高效液相色谱技术(DH-PLC)和直接测序法对30例伴家族史胃癌和8例符合家族遗传性胃癌筛选标准(ICG-HGC)的患者的血液或正常组织标本的CDH1基因进行检测.结果 16例伴胃癌家族史胃癌肿瘤组织标本CDH1阴性表达,遗传性胃癌肿瘤标本CDH1基因7个表达阴性,1个表达明显下调;伴胃癌家族史胃痛19例和遗传性胃癌6例标本表现为启动子甲基化.在30例伴家族史胃癌中2例患者发现了3个同义突变,而在遗传性胃癌的中未发现CDH1种系突变.结论 我国家族遗传性胃癌中CDH1种系突变可能并不常见,或有其他遗传易感基因参与;CDH1基因启动子区甲基化是导致了CDH1基因表达下调的主要原因.

abstractsObjective To detect the protein expression, methylatian promoter,germ-line mutations of E-Cadherin gene (CDHI) in Eight kindreds of ICG-HGC according with Intemation Collaborative Group on Hereditary Gastric Cancer standard and 30 cases of gastric carcer with gastric cancer family history in China and to investigate their possible role. Methods Eight probands diagnozed with ICG-HGC criterion and 30 cases of gastric carcer with gastric cancer family history were enrolled in our database from 1994 to 2007. Tumor tissues were checked for CDH1 expression by immunohistochemistry (IHC). CDH1 DNA se-quencing was performed for all its 16 exons in blood or normal tissues of the same patients to detect germ-line mutations. Methylation promoter study was performed by using specific primers and PCR. Results IHC analysis confirmed CDH1 apparent downregulation in all ICG-HGC probands including seven CDH1 ex-pression negative and one downregulation, whereas 16 cases of patients with gastric cancer family history CDH1 expression negative. CDH1 promoter hypermethylation was found in 19 cases with gastric cancer family history and 6 probands with ICG-HGC. DNA sequencing revealed the presence of three silent muta-tions in two patients of 30 cases with gastric cancer family history in normal tissue, thereby excluding any germ-line cells mutations in eight ICG-HGC probands probands. Conclusion CDH1 gene germ-line muta-tions may be relatively rare or have some other hereditary predisposing genes in chinese hereditary gastric cancer. CDH1 promoter hypermethylation is the main cause to lead to downregulation/disassembly of CDH1 Expression.