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

Nat Genet. 1997 Feb;15(2):170-4. doi: 10.1038/ng0297-170.


Pleiomorphic adenoma of the salivary glands is a benign epithelial tumour occurring primarily in the major and minor salivary glands. 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 frequency. 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 beta-catenin (CTNNB1), a protein interface functioning in the WG/WNT signalling pathway and specification of cell fate during embryogenesis. 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Pleomorphic / genetics*
  • Adenoma, Pleomorphic / pathology
  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Walking
  • Chromosomes, Artificial, Yeast / genetics
  • Chromosomes, Human, Pair 3 / genetics*
  • Chromosomes, Human, Pair 3 / ultrastructure
  • Chromosomes, Human, Pair 8 / genetics*
  • Chromosomes, Human, Pair 8 / ultrastructure
  • Cytoskeletal Proteins / genetics*
  • DNA-Binding Proteins / genetics*
  • Genes*
  • Humans
  • Molecular Sequence Data
  • Oncogene Proteins, Fusion / genetics*
  • Promoter Regions, Genetic*
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / pathology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Trans-Activators*
  • Translocation, Genetic / genetics*
  • Zinc Fingers / genetics*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Oncogene Proteins, Fusion
  • PLAG1 protein, human
  • PLAG1-CTNNB1 fusion protein, human
  • Trans-Activators
  • beta Catenin

Associated data

  • GENBANK/U65002
  • GENBANK/U78783