Novel germline CDH1 mutations in hereditary diffuse gastric cancer families
Novel germline CDH1 mutations in hereditary diffuse gastric cancer families
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DOI：
10.1002/humu.10067
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发表时间：
2002-01-01
期刊：
影响因子：
3.9
通讯作者：
Guilford, P
中科院分区：
文献类型：
--
作者：
Humar, B;Toro, T;Guilford, P
遗传性弥漫性胃癌（HDGC）是一种新近定义的癌症综合征，由细胞粘附蛋白E-钙粘蛋白（CDH 1）基因的失活、杂合生殖系突变引起。在这里，我们描述了在10个新发现的胃癌家族中寻找CDH 1突变。10个家庭中有7个符合HDGC的临床标准。在这7个家族中的4个中鉴定出生殖系突变，其中1个家族为临床标准的临界点。在这五个新家族中发现的突变中，有四个以前未报道过，包括两个移码突变和两个供体剪接位点突变。一个剪接位点突变发生在100%保守的+1位。第二个剪接位点突变发生在+5位置，并显示导致异常剪接。检测到的其他CDH 1变异体包括杂合-160 C-->A启动子多态性，先前已报道其与CDH 1转录降低相关。然而，我们发现这种多态性在对照人群中很常见，这表明这种多态性在胃癌易感性中的主要作用是不太可能的。
Hereditary diffuse gastric cancer (HDGC) is a recently defined cancer syndrome caused by inactivating, heterozygous germline mutations in the gene for the cell,to cell adhesion protein E-cadherin (CDH1). Here, we describe the search for CDH1 mutations in 10 newly identified gastric cancer families. Seven of 10 families met the clinical criteria for HDGC.. Germline mutations were identified in four of these seven families and one family that was borderline for the clinical criteria. Of the mutations identified in the five new families, four were previously unreported and consisted of two frameshift and two donor splice site mutations. One splice site mutation occurred at the 100% conserved +1 position. The second splice site mutation occurred at the +5 position and was shown to lead to abnormal splicing. Additional CDH1 variants detected include the heterozygous -160 C-->A promoter polymorphism, which has previously been reported to be associated with decreased CDH1 transcription. We, however, found this polymorphism to be common in a control population, suggesting that a major role for this polymorphism in gastric cancer susceptibility is unlikely.