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Mitochondrial genome analysis in penile carcinoma

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


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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Correspondence to R. B. Reis.

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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).

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