title: Genomic profiling of human penile carcinoma predicts worse prognosis and survival.
abstract: 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 copy-number 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.
authors.affiliation: CIPE-Cancer Treatment and Research Center, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Ariane F
authors.initials: AF
authors.lastname: Busso-Lopes
authors.affiliation: CIPE-Cancer Treatment and Research Center, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Fábio A
authors.initials: FA
authors.lastname: Marchi
authors.affiliation: CIPE-Cancer Treatment and Research Center, AC Camargo Cancer Center, São Paulo, Brazil. Department of Urology, Faculty of Medicine, UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Hellen
authors.initials: H
authors.lastname: Kuasne
authors.affiliation: Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo-Neto
authors.affiliation: Department of Urology, Faculty of Medicine, UNESP, Botucatu, São Paulo, Brazil.
authors.forename: José Carlos S
authors.initials: JC
authors.lastname: Trindade-Filho
authors.affiliation: Department of Urology, Faculty of Medicine, UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Carlos Márcio N
authors.initials: CM
authors.lastname: de Jesus
authors.affiliation: Department of Pelvic Surgery, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Ademar
authors.initials: A
authors.lastname: Lopes
authors.affiliation: Department of Pelvic Surgery, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Guimarães
authors.affiliation: CIPE-Cancer Treatment and Research Center, AC Camargo Cancer Center, São Paulo, Brazil. Department of Urology, Faculty of Medicine, UNESP, Botucatu, São Paulo, Brazil. rogatto@fmb.unesp.br.
authors.forename: Silvia R
authors.initials: SR
authors.lastname: Rogatto
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000821:virology; D055028:Comparative Genomic Hybridization; D018572:Disease-Free Survival; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics; D010412:Penile Neoplasms / Q000235:genetics* / Q000401:mortality / Q000821:virology; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome