Genomic Profiling of Human Penile Carcinoma Predicts Worse Prognosis and Survival

Autor(es)

Busso-Lopes, Ariane F. ^[1] ; Marchi, Fabio A. ^[1] ; Kuasne, Hellen ^{[2, 1]} ; Scapulatempo-Neto, Cristovam ^[3] ; Trindade-Filho, Jose Carlos S. ^[2] ; de Jesus, Carlos Marcio N. ^[2] ; Lopes, Ademar ^[4] ; Guimaraes, Gustavo C. ^[4] ; Rogatto, Silvia R. ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] AC Camargo Canc Ctr, CIPE Canc Treatment & Res Ctr, BR-01508010 Sao Paulo - Brazil

^[2] UNESP, Fac Med, Dept Urol, Botucatu, SP - Brazil

^[3] Barretos Canc Hosp, Dept Pathol, Barretos, SP - Brazil

^[4] AC Camargo Canc Ctr, Dept Pelv Surg, BR-01508010 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Cancer Prevention Research; v. 8, n. 2, p. 149-156, FEB 2015.
• Citações Web of Science: 20

Resumo

The molecular mechanisms underlying penile carcinoma are still poorly understood, and the detection of genetic markers would be of great benefit for these patients. In this study, we assessed the genomic profile aiming at identifying potential prognostic biomarkers in penile carcinoma. Globally, 46 penile carcinoma samples were considered to evaluate DNA copynumber alterations via array comparative genomic hybridization (aCGH) combined with human papillomavirus (HPV) genotyping. Specific genes were investigated by using qPCR, FISH, and RT-qPCR. Genomic alterations mapped at 3p and 8p were related to worse prognostic features, including advanced T and clinical stage, recurrence and death from the disease. Losses of 3p21.1-p14.3 and gains of 3q25.31-q29 were associated with reduced cancer-specific and disease-free survival. Genomic alterations detected for chromosome 3 (LAMP3, PPARG, TNFSF10 genes) and 8 (DLC1) were evaluated by qPCR. DLC1 and PPARG losses were associated with poor prognosis characteristics. Losses of DLC1 were an independent risk factor for recurrence on multivariate analysis. The gene-expression analysis showed downexpression of DLC1 and PPARG and overexpression of LAMP3 and TNFSF10 genes. Chromosome Y losses and MYC gene (8q24) gains were confirmed by FISH. HPV infection was detected in 34.8% of the samples, and 19 differential genomic regions were obtained related to viral status. At first time, we described recurrent copy-number alterations and its potential prognostic value in penile carcinomas. We also showed a specific genomic profile according to HPV infection, supporting the hypothesis that penile tumors present distinct etiologies according to virus status. (C) 2014 AACR. (AU)

• Processo FAPESP: 09/06851-7 - Variação no número de cópias genômicas e expressão gênica em larga escala em carcinomas de pênis.
• Beneficiário: Ariane Fidelis Busso Lopes
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/52088-3 - O carcinoma de pênis: estudo de um problema brasileiro abordando da morfologia aos mecanismos moleculares
• Beneficiário: José Vassallo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/51601-6 - Perfil de metilação em carcinoma de pênis
• Beneficiário: Silvia Regina Rogatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/03974-0 - Marcadores tumorais evidenciados pelas metodologias de variação no número de cópias genômicas (aCGH) e expressão gênica em larga escala em carcinomas de pênis
• Beneficiário: Ariane Fidelis Busso Lopes
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto