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Molecular Biology Reports

, Volume 45, Issue 4, pp 591–600 | Cite as

Mitochondrial genome analysis in penile carcinoma

  • L. F. Araujo
  • A. T. TerraJr.
  • C. T. G. Sares
  • C. F. R. Sobreira
  • E. F. Faria
  • R. D. Machado
  • A. A. RodriguesJr.
  • V. F. Muglia
  • W. A. SilvaJr.
  • R. B. ReisEmail author
Original Article

Abstract

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.

Keywords

Mitochondrial genome Penile carcinoma Mutation MtDNA copy number Heteroplasmy 

Notes

Acknowledgements

We would like to thank Anemari Dinarti-Santos for technical support.

Funding

This study was funded by São Paulo Research Foundation (FAPESP), Grants #2009/53853-5, #2013/25119-0, and #2013/08135-2; and by Research Support of the University Sao Paulo, CISBi-NAP/USP Grant #12.1.25441.01.2.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest in the authorship or publication of contribution.

Ethical approval

This study was previously approved by the Ethics Committee of Ribeirão Preto at University of São Paulo (Process Number 14096/2010). All patients gave their written consent to participate in this study.

Supplementary material

11033_2018_4197_MOESM1_ESM.xlsx (32 kb)
Supplementary material 1 (XLSX 32 KB)
11033_2018_4197_MOESM2_ESM.docx (116 kb)
Supplementary material 2 (DOCX 115 KB)

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • L. F. Araujo
    • 1
    • 2
  • A. T. TerraJr.
    • 3
  • C. T. G. Sares
    • 3
  • C. F. R. Sobreira
    • 4
  • E. F. Faria
    • 5
  • R. D. Machado
    • 5
  • A. A. RodriguesJr.
    • 3
  • V. F. Muglia
    • 6
  • W. A. SilvaJr.
    • 1
    • 2
    • 7
  • R. B. Reis
    • 3
    • 7
    • 8
    Email author
  1. 1.Department of Genetics at Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  2. 2.National Institute of Science and Technology in Stem Cell and Cell Therapy, and Center for Cell-based Therapy-CEPID/FAPESPRibeirão PretoBrazil
  3. 3.Hospital das Clinicas, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  4. 4.Department of Neuroscience, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  5. 5.Department of UrologyBarretos Cancer HospitalBarretosBrazil
  6. 6.Center of Imaging Sciences and Medical Physics, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  7. 7.Center for Medical Genomics, HCFMRP/USP, and Center for Integrative System Biology - CISBi-NAP/USPUniversity of São PauloRibeirão PretoBrazil
  8. 8.Division of Urology, Department of Surgery, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil

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