CDH1 gene mutations do not contribute in hereditary diffuse gastric cancer in Poland
CDH1 gene mutations do not contribute in hereditary diffuse gastric cancer in Poland
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DOI：
10.1007/s10689-010-9381-2
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发表时间：
2010-12-01
期刊：
影响因子：
2.2
通讯作者：
Lubinski, Jan
中科院分区：
文献类型：
--
作者：
Jakubowska, Anna;Lawniczak, Malgorzata;Lubinski, Jan
遗传性弥漫性胃癌(HDGC)是一种以弥漫性胃癌和小叶性乳腺癌的高危为特征的癌症易感综合征。HDGC是由编码E-钙粘附素的CDH1基因的胚系突变引起的，E-钙粘附素是负责钙依赖的细胞间黏附的跨膜糖蛋白家族的成员，在维持细胞分化和上皮组织的正常结构方面发挥着重要作用。在符合HDGC强大临床标准的家系中，30-46%的家系中检测到CDH1基因突变，在满足修改后的标准的家系中，检测到约11%的突变。在本研究中，我们研究了波兰HDGC患者中CDH1基因的胚系突变。对符合HDGC标准的86例波兰癌症患者进行了CDH1基因全序列测序分析。我们在56例患者中发现了几个沉默突变，其中包括一个常见的突变(c.2076T>；C)，在2例患者中发现了三个罕见的突变(c.2253C>；T，c.1896C>；T，c.2634C>；T)。此外，我们还在内含子中发现了四个未知意义的稀有序列变异。我们没有检测到任何有害的CDH1基因突变。根据修订的临床标准，患有HDGC的波兰家庭中不存在CDH1基因突变。需要对符合HDGC限制性标准的HDGC家系进行进一步研究。
Hereditary diffuse gastric cancer (HDGC) is a cancer susceptibility syndrome characterized by a high risk of diffuse stomach cancer and lobular breast cancer. HDGC is caused by germline mutations in the CDH1 gene encoding the E-cadherin which is a member of the transmembrane glycoprotein family responsible for calcium-dependent, cell-to-cell adhesion and plays a fundamental role in the maintenance of cell differentiation and the normal architecture of epithelial tissues. Mutations in the CDH1 gene are detected in 30-46% of families that fulfil strong clinical criteria for HDGC and in about 11% of families fulfilling the modified criteria. In the present study, we investigated germline mutations in the CDH1 gene in Polish patients with HDGC. The entire coding sequence of CDH1 gene was analyzed by sequencing in 86 Polish cancer patients from families fulfilling the modified criteria of HDGC. We found several silent mutations including one common variant (c.2076T > C) present in 56 patients, and three rare variants (c.2253C > T, c.1896C > T, c.2634C > T) detected in 2 patients. In addition, we found four rare sequence variants of unknown significance localized in introns. We did not detect any deleterious mutations of the CDH1 gene. CDH1 gene mutations are not present in Polish families with HDGC defined by the modified clinical criteria. Further studies of families with HDGC matching the restrictive criteria for HDGC are needed.