title: Sequence variants and haplotype analysis of cat ERBB2 gene: a survey on spontaneous cat mammary neoplastic and non-neoplastic lesions.
abstract: The human ERBB2 proto-oncogene is widely considered a key gene involved in human breast cancer onset and progression. Among spontaneous tumors, mammary tumors are the most frequent cause of cancer death in cats and second most frequent in humans. In fact, naturally occurring tumors in domestic animals, more particularly cat mammary tumors, have been proposed as a good model for human breast cancer, but critical genetic and molecular information is still scarce. The aims of this study include the analysis of the cat ERBB2 gene partial sequences (between exon 17 and 20) in order to characterize a normal and a mammary lesion heterogeneous populations. Cat genomic DNA was extracted from normal frozen samples (n = 16) and from frozen and formalin-fixed paraffin-embedded mammary lesion samples (n = 41). We amplified and sequenced two cat ERBB2 DNA fragments comprising exons 17 to 20. It was possible to identify five sequence variants and six haplotypes in the total population. Two sequence variants and two haplotypes show to be specific for cat mammary tumor samples. Bioinformatics analysis predicts that four of the sequence variants can produce alternative transcripts or activate cryptic splicing sites. Also, a possible association was identified between clinicopathological traits and the variant haplotypes. As far as we know, this is the first attempt to examine ERBB2 genetic variations in cat mammary genome and its possible association with the onset and progression of cat mammary tumors. The demonstration of a possible association between primary tumor size (one of the two most important prognostic factors) and the number of masses with the cat ERBB2 variant haplotypes reveal the importance of the analysis of this gene in veterinary medicine.
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro (IBB, CGB-UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Santos
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro (IBB, CGB-UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal.|Department of Genetics and Biotechnology, University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801 Vila Real, Portugal.
authors.forename: Estela
authors.initials: E
authors.lastname: Bastos
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro (IBB, CGB-UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal.|Department of Veterinary Clinics, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Largo Professor Abel Salazar, 2, 4099-003 Porto, Portugal.
authors.forename: Cláudia S
authors.initials: CS
authors.lastname: Baptista
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro (IBB, CGB-UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sá
authors.affiliation: CEA/DSV/IG-Centre National de Génotypage, Bâtiment G2, 2 rue Gaston Crémieux, CP 5721, 91057 Evry Cedex, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Caloustian
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro (IBB, CGB-UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Guedes-Pinto
authors.affiliation: Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal.|Institute of Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Gärtner
authors.affiliation: CEA/DSV/IG-Centre National de Génotypage, Bâtiment G2, 2 rue Gaston Crémieux, CP 5721, 91057 Evry Cedex, France.
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Gut
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro (IBB, CGB-UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal.|Department of Genetics and Biotechnology, University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801 Vila Real, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Chaves
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002415:Cats; D005260:Female; D018734:Genes, erbB-2; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology*; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human