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Mitochondrial genome instability in colorectal adenoma and adenocarcinoma

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Tumor Biology

Abstract

Mitochondrial dysfunction is regarded as a hallmark of cancer progression. In the current study, we evaluated mitochondrial genome instability and copy number in colorectal cancer using Next Generation Sequencing approach and qPCR, respectively. The results revealed higher levels of heteroplasmy and depletion of the relative mtDNA copy number in colorectal adenocarcinoma. Adenocarcinoma samples also presented an increased number of mutations in nuclear genes encoding proteins which functions are related with mitochondria fusion, fission and localization. Moreover, we found a set of mitochondrial and nuclear genes, which cooperate in the same mitochondrial function simultaneously mutated in adenocarcinoma. In summary, these results support an important role for mitochondrial function and genomic instability in colorectal tumorigenesis.

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Acknowledgments

We thank Adriana Aparecida Marques and Life Technologies (Brazil) for the technical support. We also thank Vinicius Kannen Cardoso for the scientific insights.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

This work was funding by The National Council for Scientific and Technological Development (CNPq), grant #573754/2008-0; by grants #2008/57877-3 and #2013/08135-2, São Paulo Research Foundation (FAPESP); and by Research Support of the University Sao Paulo, CISBi-NAP/USP #12.1.25441.01.2.

Conflicts of interest

None.

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Authors and Affiliations

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

    Luiza F. de Araujo, Aline S. Fonseca, Bruna R Muys, Rafaela B. L. Bueno, Julio C. C. Lorenzi, Greice A. Molfetta, Dalila L. Zanette & Wilson A. Silva Jr

  2. Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil

    Luiza F. de Araujo, Aline S. Fonseca, Bruna R Muys, Jessica R. Plaça, Rafaela B. L. Bueno, Julio C. C. Lorenzi, Anemari R. D. Santos, Greice A. Molfetta, Dalila L. Zanette, Jorge E. S. Souza, Valeria Valente & Wilson A. Silva Jr

  3. Center for Medical Genomics (HCFMRP/USP), Center for Integrative Systems Biology (CISBi – NAP/USP), Ribeirão Preto, Brazil

    Greice A. Molfetta, Dalila L. Zanette, Jorge E. S. Souza, Valeria Valente & Wilson A. Silva Jr

  4. Department of Clinical Analysis, Faculty of Pharmaceutical Science of Araraquara, University of São Paulo State, Araraquara, Brazil

    Valeria Valente

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  1. Luiza F. de Araujo
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  2. Aline S. Fonseca
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  3. Bruna R Muys
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  12. Wilson A. Silva Jr
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Correspondence to Wilson A. Silva Jr.

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de Araujo, L.F., Fonseca, A.S., Muys, B.R. et al. Mitochondrial genome instability in colorectal adenoma and adenocarcinoma. Tumor Biol. 36, 8869–8879 (2015). https://doi.org/10.1007/s13277-015-3640-7

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