Tumor Biology

, Volume 36, Issue 11, pp 8869–8879 | Cite as

Mitochondrial genome instability in colorectal adenoma and adenocarcinoma

  • 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. SilvaJr
Research Article

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.

Keywords

Mitochondrial genome Colorectal cancer Heteroplasmy Genome instability 

Notes

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.

Supplementary material

13277_2015_3640_MOESM1_ESM.docx (179 kb)
ESM 1 (DOCX 178 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Luiza F. de Araujo
    • 1
    • 2
  • Aline S. Fonseca
    • 1
    • 2
  • Bruna R Muys
    • 1
    • 2
  • Jessica R. Plaça
    • 2
  • Rafaela B. L. Bueno
    • 1
    • 2
  • Julio C. C. Lorenzi
    • 1
    • 2
  • Anemari R. D. Santos
    • 2
  • Greice A. Molfetta
    • 1
    • 2
    • 3
  • Dalila L. Zanette
    • 1
    • 2
    • 3
  • Jorge E. S. Souza
    • 2
    • 3
  • Valeria Valente
    • 2
    • 3
    • 4
  • Wilson A. SilvaJr
    • 1
    • 2
    • 3
  1. 1.Department of Genetics, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  2. 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 PretoRiberão PretoBrazil
  3. 3.Center for Medical Genomics (HCFMRP/USP)Center for Integrative Systems Biology (CISBi – NAP/USP)Ribeirão PretoBrazil
  4. 4.Department of Clinical Analysis, Faculty of Pharmaceutical Science of AraraquaraUniversity of São Paulo StateAraraquaraBrazil

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