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Promoter swapping between the genes for a novel zinc finger protein and β-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations

Nature Genetics volume 15, pages 170–174 (1997)Cite this article

An Erratum to this article was published on 01 April 1997

Abstract

Pleiomorphic adenoma of the salivary glands is a benign epithelial tumour occurring primarily in the major and minor salivary glands1. It is by far the most common type of salivary gland tumour. Microscopically, pleiomorphic adenomas show a marked histological diversity with epithelial, myoepithelial and mesenchymal components in a variety of patterns. In addition to a cytogenetic subgroup with normal karyotypes, pleiomorphic adenomas are characterized by recurrent chromosome rearrangements, particularly reciprocal translocations, with breakpoints at 8q12, 3p21, and 12q13–15, in that order of frequency2,3. The most common abnormality is a reciprocal t(3;8)(p21;q12). We here demonstrate that the t(3;8)(p21;q12) results in promoter swapping between PLAG1, a novel, developmentally regulated zinc finger gene at 8q12, and the constitutively expressed gene for β-catenin (CTNNB1), a protein interface functioning in the WG/WNT signalling pathway and specification of cell fate during embryogenesis4. Fusions occur in the 5′-non-coding regions of both genes, exchanging regulatory control elements while preserving the coding sequences. Due to the t(3;8)(p21;q12), PLAG1 is activated and expression levels of CTNNB1 are reduced. Activation of PLAG1 was also observed in an adenoma with a variant translocation t(8;15)(q12;q14). Our results indicate that PLAG1 activation due to promoter swapping is a crucial event in salivary gland tumourigenesis.

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Authors and Affiliations

  1. Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven & Flanders Interuniversity Institute for Biotechnology, Herestraat 49, B-3000, Leuven, Belgium

    Koen Kas, Marianne L. Voz, Eva Meyen & Wim J.M. Van de Ven

  2. Laboratory of Cancer Genetics, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, S-413 45, Göteborg, Sweden

    Eva Röijer, Anna-Karin Åström & Göran Stenman

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  1. Koen Kas
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Kas, K., Voz, M., Röijer, E. et al. Promoter swapping between the genes for a novel zinc finger protein and β-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations. Nat Genet 15, 170–174 (1997). https://doi.org/10.1038/ng0297-170

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