Mitochondrial genome analysis in penile carcinoma

Autor(es)

Araujo, L. F. ^{[1, 2, 3]} ; Terra, Jr., A. T. ^[4] ; Sares, C. T. G. ^[4] ; Sobreira, C. F. R. ^[5] ; Faria, E. F. ^[6] ; Machado, R. D. ^[6] ; Rodrigues, Jr., A. A. ^[4] ; Muglia, V. F. ^[7] ; Silva, Jr., W. A. ^{[1, 2, 3, 8, 9]} ; Reis, R. B. ^{[4, 8, 9, 10]}

Afiliação do(s) autor(es)

^[1] Natl Inst Sci & Technol Stem Cell & Cell Therapy, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil

^[3] Ctr Cell Based Therapy CEPID FAPESP, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Hosp Clin, Ribeirao Preto - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci, Ribeirao Preto, SP - Brazil

^[6] Barretos Canc Hosp, Dept Urol, Barretos, SP - Brazil

^[7] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Imaging Sci & Med Phys, Ribeirao Preto, SP - Brazil

^[8] Univ Sao Paulo, Ctr Med Genom, HCFMRP USP, Ribeirao Preto, SP - Brazil

^[9] Univ Sao Paulo, Ctr Integrat Syst Biol CISBi NAP USP, Ribeirao Preto, SP - Brazil

^[10] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg, Div Urol, Av Bandeirantes 3900, 9th Floor, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR BIOLOGY REPORTS; v. 45, n. 4, p. 591-600, AUG 2018.
• Citações Web of Science: 1

Resumo

Penile cancer is a rare neoplasm that seems to be linked to socio-economic differences. Mitochondrial genome alterations are common in many tumors types and are reported as regulating oxidative metabolism and impacting tumorigenesis. In this study, we evaluate for the first time the mitochondrial genome in penile carcinoma (PeCa), aiming to evaluate heteroplasmy, mitochondrial DNA (mtDNA) mutational load and mtDNA content in Penile tumors. Using next generation sequencing (NGS), we sequenced the mitochondrial genome of 13 penile tumors and 12 non-neoplastic tissue samples, which allowed us to identify mtDNA variants and heteroplasmy. We further evaluated variant's pathogenicity using Mutpred predictive software and calculated mtDNA content using quantitative PCR. Mitochondrial genome sequencing revealed an increase number of non-synonymous variants in the tumor tissue, along with higher frequency of heteroplasmy and mtDNA depletion in penile tumors, suggesting an increased mitochondrial instability in penile tumors. We also described a list of mitochondrial variants found in penile tumor and normal tissue, including five novel variants found in the tumoral tissue. Our results showed an increased mitochondrial genome instability in penile tumors. We also suggest that mitochondrial DNA copy number (mtDNAcn) and mtDNA variants may act together to imbalance mitochondrial function in PeCa. The better understanding of mitochondrial biology can bring new insights on mechanisms and open a new field for therapy in PeCa. (AU)

• Processo FAPESP: 13/25119-0 - Estudo do metabolismo energético na progressão do melanoma com base na instabilidade do genoma mitocondrial
• Beneficiário: Luíza Ferreira de Araújo
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/53853-5 - Aquisição de uma plataforma de alta performance para análises computacionais aplicadas à medicina
• Beneficiário: Wilson Araújo da Silva Junior
• Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs