International Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Medical University, ul Połabska 4, 70-115 Szczecin, Poland.
Fam Cancer. 2010 Dec;9(4):605-8. doi: 10.1007/s10689-010-9381-2.
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.
遗传性弥漫性胃癌(HDGC)是一种癌症易感性综合征,其特征是弥漫性胃癌和小叶性乳腺癌的风险较高。HDGC 是由 CDH1 基因的种系突变引起的,该基因编码 E-钙黏蛋白,是跨膜糖蛋白家族的成员,负责钙依赖性、细胞间黏附,并在维持细胞分化和上皮组织的正常结构中发挥着基本作用。在满足 HDGC 强烈临床标准的 30-46%的家族中以及在满足改良标准的约 11%的家族中检测到 CDH1 基因突变。在本研究中,我们研究了波兰 HDGC 患者中 CDH1 基因的种系突变。通过对 86 名来自满足 HDGC 改良标准的家族的波兰癌症患者进行测序,分析了 CDH1 基因的整个编码序列。我们发现了一些沉默突变,包括存在于 56 名患者中的一个常见变体(c.2076T>C),以及在 2 名患者中检测到的三个罕见变体(c.2253C>T、c.1896C>T、c.2634C>T)。此外,我们还发现了四个位于内含子中的未知意义的罕见序列变体。我们没有检测到 CDH1 基因的任何有害突变。CDH1 基因突变不存在于波兰符合改良临床标准的 HDGC 家族中。需要对符合 HDGC 限制性标准的 HDGC 家族进行进一步研究。
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