Autor(es): Laufer-Amorim, Renée [UNESP] ; Fonseca-Alves, Carlos Eduardo [UNESP] ; Villacis, Rolando Andre Rios ; Linde, Sandra Aparecida Drigo [UNESP] ; Carvalho, Marcio [UNESP] ; Larsen, Simon Jonas ; Marchi, Fabio Albuquerque ; Rogatto, Silvia Regina
Data: 2019
Identificador Persistente: http://hdl.handle.net/11449/188936
Origem: Oasisbr
Assunto(s): Comparative oncology; Copy number alteration; Dog; Microarray; Proliferative inflammatory atrophy; Prostate cancer
Made available in DSpace on 2019-10-06T16:23:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-04-01
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Canine carcinomas have been considered natural models for human diseases; however, the genomic profile of canine prostate cancers (PCs) has not been explored. In this study, 14 PC androgen-receptor-negative cases, 4 proliferative inflammatory atrophies (PIA), and 5 normal prostate tissues were investigated by array-based comparative genomic hybridization (aCGH). Copy number alterations (CNAs) were assessed using the Canine Genome CGH Microarray 4 × 44K (Agilent Technologies). Genes covered by recurrent CNAs were submitted to enrichment and cross-validation analysis. In addition, the expression levels of TP53, MDM2 and ZBTB4 were evaluated in an independent set of cases by qPCR. PC cases presented genomic complexity, while PIA samples had a small number of CNAs. Recurrent losses covering well-known tumor suppressor genes, such as ATM, BRCA1, CDH1, MEN1 and TP53, were found in PC. The in silico functional analysis showed several cancer-related genes associated with canonical pathways and interaction networks previously described in human PC. The MDM2, TP53, and ZBTB4 copy number alterations were translated into altered expression levels. A cross-validation analysis using The Cancer Genome Atlas (TCGA) database for human PC uncovered similarities between canine and human PCs. Androgen-receptor-negative canine PC is a complex disease characterized by high genomic instability, showing a set of genes with similar alterations to human cancer.
Department of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University-UNESP
Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University-UNESP
Department of Genetics and Morphology Institute of Biological Sciences University of Brasília-UnB
Department of Mathematics and Computer Science University of Southern Denmark
International Research Center (CIPE) A.C. Camargo Cancer Center
Department of Clinical Genetics Vejle Hospital Institute of Regional Health Research University of Southern Denmark
Department of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University-UNESP
Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University-UNESP
FAPESP: 2008/57221-0
FAPESP: 2015/25400-7
