Comprehensive Genomic Profiling of Androgen-Receptor-Negative Canine Prostate Cancer

Autor(es)

Laufer-Amorim, Renee ; Fonseca-Alves, Carlos Eduardo ; Rios Villacis, Rolando Andre ; Drigo Linde, Sandra Aparecida ; Carvalho, Marcio ; Larsen, Simon Jonas ; Marchi, Fabio Albuquerque ; Rogatto, Silvia Regina

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 7, p. 14-pg., 2019-03-28.

Resumo

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 x 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. (AU)

• Processo FAPESP: 15/25400-7 - Estudo para caracterização in vitro e molecular de células prostáticas caninas e avaliação da resposta antitumoral a drogas alvo dirigidas
• Beneficiário: Carlos Eduardo Fonseca Alves
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 08/57221-0 - Alteracoes no numero de copias genomicas em lesoes pre-neoplasicas e neoplasicas da prostata do cao
• Beneficiário: Renee Laufer Amorim
• Modalidade de apoio: Auxílio à Pesquisa - Regular