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

Oncogene volume 23, pages 2236–2240 (2004)Cite this article

Abstract

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.

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Acknowledgements

This study was funded by grants from Fundação para a Ciência e a Tecnologia, Portugal (Project: POCTI/35374/CBO/2000 and POCTI/CBO/40820/2001).

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Author notes

  1. Carla Oliveira and Joyce de Bruin: We wish it to be known that, in our opinion, the first two authors should be regarded as joint first authors

Authors and Affiliations

  1. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, 4200-465, Portugal

    Carla Oliveira, Sérgio Nabais, Cátia Moutinho, Raquel Seruca & Fátima Carneiro

  2. Department of Pathology, University Medical Centre Nijmegen, Nijmegen, 6500 HB, The Netherlands

    Joyce de Bruin, Marjolijn Ligtenberg & Han van Krieken

  3. Department of Human Genetics, University Medical Centre Nijmegen, Nijmegen, 6500 HB, The Netherlands

    Marjolijn Ligtenberg

  4. Department of Gastroenterology, University Medical Centre Nijmegen, Nijmegen, 6500 HB, The Netherlands

    Fokko M Nagengast

  5. Medical Faculty of the University of Porto, Porto, 4200-465, Portugal

    Raquel Seruca & Fátima Carneiro

Authors
  1. Carla Oliveira
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  2. Joyce de Bruin
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Correspondence to Carla Oliveira.

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Oliveira, C., de Bruin, J., Nabais, S. et al. Intragenic deletion of CDH1 as the inactivating mechanism of the wild-type allele in an HDGC tumour. Oncogene 23, 2236–2240 (2004). https://doi.org/10.1038/sj.onc.1207335

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