【摘要】 目的　研究遗传性弥漫型胃癌上皮型钙黏素基因 (CDH1)种系突变情况。方法　对符合初筛标准的 5个胃癌家系 (A、B、C、E、F)先证者取血 ,提取基因组DNA ,利用PCR方法扩增上皮型钙黏素基因的 16个外显子 ,以变性高效液相色谱技术检测 ,对可疑突变者双向测序。结果　B家系先证者CDH1基因第 10号外显子 15 0 7位碱基出现杂合性C→T转换 ,导致编码谷氨酸的密码子CAG转变为终止密码子UAG ,从而产生截短蛋白。该先证者异时性患有乳腺侵润性小叶腺癌和弥漫型胃癌 ,免疫组化研究显示乳腺癌组织中上皮型钙黏素表达完全缺失 ,表明乳腺癌组织中CDH1基因完全失活。结论　中国胃癌家系中存在遗传性弥漫型胃癌家系 ,并检测到一种新的CDH1基因种系截短突变 ,乳腺侵润性小叶腺癌可能系遗传性弥漫型胃癌肿瘤谱的一部分。更多还原

【Abstract】 Objective To evaluate the frequency and nature of E cadherin gene (CDH1) germline mutations in familial gastric cancer kindreds of china. Methods Five familial gastric cancer kindreds of Chinese origin were screened for germline CDH1 mutations, all of them meeting the clinical criteria for hereditary diffuse gastric cancer (HDGC), by PCR DHPLC and direct sequencing. Results A new truncating mutation in exon 10 in B family was identified, producing a stop codon at position 503 (Q503X), resulting in a truncated protein. The proband of this family had metachronous development of lobular breast and diffuse type gastric carcinoma. No protein expression was detected in the lobular breast carcinoma, indicating complete inactivation of the gene. Conclusions A Chinese gastric cancer family with CDH1 germline truncating mutation is described for the first time, and our findings suggest that lobular breast carcinoma might be part of the tumor spectrum of HDGC.更多还原