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Mitochondrial genome analysis in penile carcinoma

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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.

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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.

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Authors and Affiliations

  1. Department of Genetics at Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    L. F. Araujo & W. A. Silva Jr.

  2. National Institute of Science and Technology in Stem Cell and Cell Therapy, and Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, São Paulo, Brazil

    L. F. Araujo & W. A. Silva Jr.

  3. Hospital das Clinicas, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

    A. T. Terra Jr., C. T. G. Sares, A. A. Rodrigues Jr. & R. B. Reis

  4. Department of Neuroscience, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    C. F. R. Sobreira

  5. Department of Urology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

    E. F. Faria & R. D. Machado

  6. Center of Imaging Sciences and Medical Physics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    V. F. Muglia

  7. Center for Medical Genomics, HCFMRP/USP, and Center for Integrative System Biology - CISBi-NAP/USP, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    W. A. Silva Jr. & R. B. Reis

  8. Division of Urology, Department of Surgery, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, 9th floor, Ribeirão Preto, São Paulo, Brazil

    R. B. Reis

Authors
  1. L. F. Araujo
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  2. A. T. Terra Jr.
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  3. C. T. G. Sares
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  4. C. F. R. Sobreira
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  5. E. F. Faria
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  6. R. D. Machado
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  7. A. A. Rodrigues Jr.
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  8. V. F. Muglia
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  9. W. A. Silva Jr.
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  10. R. B. Reis
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Corresponding author

Correspondence to R. B. Reis.

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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.

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Araujo, L.F., Terra, A.T., Sares, C.T.G. et al. Mitochondrial genome analysis in penile carcinoma. Mol Biol Rep 45, 591–600 (2018). https://doi.org/10.1007/s11033-018-4197-5

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  • DOI: https://doi.org/10.1007/s11033-018-4197-5

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