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

Reference : Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in ...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Genetics & genetic processes
	To cite this reference:	http://hdl.handle.net/2268/135355

Title :	Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations.
Language :	English
Author, co-author :	Kas, K. [> > > >]
	Voz, Marianne [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
	Roijer, E. [> > > >]
	Astrom, A. K. [> > > >]
	Meyen, E. [> > > >]
	Stenman, G. [> > > >]
	Van de Ven, W. J. [> > > >]
Publication date :	1997
Journal title :	Nature Genetics
Publisher :	Nature Publishing Group
Volume :	15
Issue/season :	2
Pages :	170-4
Audience :	International
ISSN :	1061-4036
e-ISSN :	1546-1718
City :	New York
Country :	NY
Keywords :	[en] Adenoma, Pleomorphic/genetics/pathology ; Amino Acid Sequence ; Base Sequence ; Chromosome Walking ; Chromosomes, Artificial, Yeast/genetics ; Chromosomes, Human, Pair 3/genetics/ultrastructure ; Chromosomes, Human, Pair 8/genetics/ultrastructure ; Cytoskeletal Proteins/genetics ; DNA-Binding Proteins/genetics ; Genes ; Humans ; Molecular Sequence Data ; Oncogene Proteins, Fusion/genetics ; Promoter Regions, Genetic ; Salivary Gland Neoplasms/genetics/pathology ; Sequence Alignment ; Sequence Homology, Amino Acid ; Trans-Activators ; Translocation, Genetic/genetics ; Zinc Fingers/genetics ; beta Catenin
Abstract :	[en] 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.
Permalink :	http://hdl.handle.net/2268/135355
DOI :	10.1038/ng0297-170

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