Sequence variants and haplotype analysis of cat ERBB2 gene: a survey on spontaneous cat mammary neoplastic and non-neoplastic lesions

• Published in: International journal of molecular sciences Vol. 13; no. 3; pp. 2783 - 2800
• Main Authors: Santos, Sara, Bastos, Estela, Baptista, Cláudia S, Sá, Daniela, Caloustian, Christophe, Guedes-Pinto, Henrique, Gärtner, Fátima, Gut, Ivo G, Chaves, Raquel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-03-2012; Molecular Diversity Preservation International (MDPI)
• Subjects: Alternative Splicing - genetics; Animals; Base Sequence; Bioinformatics; Biotechnology; Breast cancer; Cat Mammary Tumors (CMT); Cats; Cell division; DNA; Domestic animals; Electronic mail systems; ErbB-2 protein; Exons; Female; Gene amplification; Genes, erbB-2; Genomes; genomics; Genotype; Haplotypes; Haplotypes - genetics; Histopathology; Humans; Immunology; Kinases; Leukemia; Lymphatic system; Mammary gland; Mammary Neoplasms, Animal - genetics; Mammary Neoplasms, Animal - pathology; Medical prognosis; Metastasis; Molecular modelling; Molecular Sequence Data; Mutation; Nucleotide sequence; Proteins; Proto-oncogenes; Receptor, ErbB-2 - genetics; Sequence Analysis, DNA; Sequence Variants (SVs); Splicing; Splicing Sites (SS); Tumors; v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2); Veterinary medicine; Portugal; Haplotypes; Cat Mammary Tumors (CMT); v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2); Splicing Sites (SS); Sequence Variants (SVs)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms13032783

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.