Mutations of the human E-cadherin (CDH1) gene

Authors

  • Geert Berx,

    1. Department of Molecular Biology, Molecular Cell Biology Unit, V.I.B., University of Gent, B-9000 Gent, Belgium
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  • Karl-Friedrich Becker,

    1. Technische Universität, Klinikum rechts der Isar, Institut für Pathologie, Ismaninger Strasse 22, D-81675 München, Germany, and GSF-National Research Center for Environment and Health, Institute of Pathology, D-85764 Neuherberg, Germany
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  • Heinz Höfler,

    1. Technische Universität, Klinikum rechts der Isar, Institut für Pathologie, Ismaninger Strasse 22, D-81675 München, Germany, and GSF-National Research Center for Environment and Health, Institute of Pathology, D-85764 Neuherberg, Germany
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  • Frans van Roy

    Corresponding author
    1. Department of Molecular Biology, Molecular Cell Biology Unit, V.I.B., University of Gent, B-9000 Gent, Belgium
    • Department of Molecular Biology, Molecular Cell Biology Unit, V.I.B., University of Gent, Ledeganckstraat 35, B-9000 Gent, Belgium; Fax: 32-9-2645331
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Abstract

The cell–cell adhesion molecule E-cadherin is well known to act as a strong invasion suppressor in experimental tumor cell systems. Frequent inactivating mutations have been identified for the E-cadherin gene (CDH1) in diffuse gastric cancers and lobular breast cancers. To date, 69 somatic mutations have been reported comprising, in addition to few missense mutations, mainly splice site mutations and truncation mutations caused by insertions, deletions, and nonsense mutations. Interestingly, there is a major difference in mutation type between diffuse gastric and infiltrative lobular breast cancers. In diffuse gastric tumors, the predominant defects are exon skippings, which cause in-frame deletions. By contrast, most mutations found in infiltrating lobular breast cancers are out-of-frame mutations, which are predicted to yield secreted truncated E-cadherin fragments. In most cases, these mutations do occur in combination with loss of heterozygosity (LOH) of the wild-type allele. Inactivating germline mutations of E-cadherin were recently reported for families with early-onset diffuse gastric cancer. Also, at the early stages of sporadic lobular breast and diffuse gastric cancers, E-cadherin mutations were detected, suggesting loss of growth control by such mutations and defining E-cadherin as a true tumor suppressor for these particular tumor types. Hum Mutat 12:226–237, 1998. © 1998 Wiley-Liss, Inc.

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