title: Intragenic deletion of CDH1 as the inactivating mechanism of the wild-type allele in an HDGC tumour.
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.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-465 Porto, Portugal. carlaol@ipatimup.pt
authors.forename: Carla
authors.initials: C
authors.lastname: Oliveira
authors.forename: Joyce
authors.initials: J
authors.lastname: de Bruin
authors.forename: Sérgio
authors.initials: S
authors.lastname: Nabais
authors.forename: Marjolijn
authors.initials: M
authors.lastname: Ligtenberg
authors.forename: Cátia
authors.initials: C
authors.lastname: Moutinho
authors.forename: Fokko M
authors.initials: FM
authors.lastname: Nagengast
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Han
authors.initials: H
authors.lastname: van Krieken
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
mesh_terms: D017668:Age of Onset; D000483:Alleles; D001706:Biopsy; D015820:Cadherins / Q000235:genetics*; D018279:Carcinoma, Signet Ring Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004724:Endoscopy; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006580:Genetic Carrier Screening; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D010375:Pedigree; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D044465:White People
chemical_list: D015820:Cadherins