PROMOTER SWAPPING BETWEEN THE GENES FOR A NOVEL ZINC-FINGER PROTEIN AND BETA-CATENIN IN PLEIOMORPHIC ADENOMAS WITH T(3-8)(P21-Q12) TRANSLOCATIONS

Pleiomorphic adenoma of the salivary glands is a benign epithelial tum our occurring primarily in the major and minor salivary glands(1). It is by far the most common type of salivary gland tumour. Microscopical ly, pleiomorphic adenomas show a marked histological diversity with ep ithelial, myoepithelial and mesenchymal components in a variety of pat terns. In addition to a cytogenetic subgroup with normal karyotypes, p leiomorphic adenomas are characterized by recurrent chromosome rearran gements, particularly reciprocal translocations, with breakpoints at 8 q12, 3p21, and 12q13-15, in that order of frequency(2,3). The most com mon abnormality is a reciprocal t(3;8)(p21;q12). We here demonstrate t hat the t(3;8)(p21;q12) results in promoter swapping between PLAG1, a novel, developmentally regulated zinc finger gene at 8q12, and the con stitutively expressed gene for beta-catenin (CTNNB1), a protein interf ace functioning in the WG/WNT signalling pathway and specification of cell fate during embryogenesis(4). Fusions occur in the 5'-non-coding regions of both genes, exchanging regulatory control elements while pr eserving the coding sequences. Due to the t(3;8)(p21;q12), PLAG1 is ac tivated and expression levels of CTNNB1 are reduced. Activation of PLA G1 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.