Intragenic deletion of CDH1 as the inactivating mechanism of the wild-type allele in an HDGC tumour

被引:74
作者
Oliveira, C [1 ]
de Bruin, J
Nabais, S
Ligtenberg, M
Moutinho, C
Nagengast, FM
Seruca, R
van Krieken, H
Carneiro, F
机构
[1] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200465 Oporto, Portugal
[2] Univ Med Ctr Nijmegen, Dept Pathol, NL-6500 HB Nijmegen, Netherlands
[3] Univ Med Ctr Nijmegen, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands
[4] Univ Med Ctr Nijmegen, Dept Gastroenterol, NL-6500 HB Nijmegen, Netherlands
[5] Univ Porto, Fac Med, P-4200465 Oporto, Portugal
关键词
E-cadherin; hereditary diffuse gastric cancer; HDGC; mutation; intragenic deletion; second hit;
D O I
10.1038/sj.onc.1207335
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mutations in CDH1, encoding E- cadherin, are the underlying genetic defect in approximately one- third of the hereditary diffuse gastric cancer ( HDGC) families described so far. Tumours arising in these families show abnormal or absence of E- cadherin expression, following the model of tumour suppressor gene inactivation. A single study has been reported showing inactivation of the CDH1 wild- type allele in tumour cells from HDGC families either by promoter methylation or by somatic mutation. In order to find the genetic alteration responsible for the presence of diffuse gastric cancers in four members of a Caucasian family, we have screened the coding sequence of CDH1 for germline mutations and searched for the second inactivating hit in the tumour samples. In this family, we have found a germline splice- site mutation in all members affected by gastric cancer and, in one tumour, a somatic deletion affecting at least exon 8 of CDH1. Our results show that a CDH1 intragenic deletion is the second hit inactivating the wild- type allele, in one of the tumours in this family.
引用
收藏
页码:2236 / 2240
页数:5
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