Short Report

Oncogene (2004) 23, 2236–2240. doi:10.1038/sj.onc.1207335 Published online 8 December 2003

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

Carla Oliveira1,6, Joyce de Bruin2,6, Sérgio Nabais1, Marjolijn Ligtenberg2,3, Cátia Moutinho1, Fokko M Nagengast4, Raquel Seruca1,5, Han van Krieken2 and Fátima Carneiro1,5

  1. 1Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-465 Porto, Portugal
  2. 2Department of Pathology, University Medical Centre Nijmegen, 6500 HB Nijmegen, The Netherlands
  3. 3Department of Human Genetics, University Medical Centre Nijmegen, 6500 HB Nijmegen, The Netherlands
  4. 4Department of Gastroenterology, University Medical Centre Nijmegen, 6500 HB Nijmegen, The Netherlands
  5. 5Medical Faculty of the University of Porto, 4200-465 Porto, Portugal

Correspondence: C Oliveira, E-mail:

6We wish it to be known that, in our opinion, the first two authors should be regarded as joint first authors

Received 30 July 2003; Revised 3 November 2003; Accepted 11 November 2003.



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.


E-cadherin, hereditary diffuse gastric cancer, HDGC, mutation, intragenic deletion, second hit