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mtDNA mutations in tumors of the central nervous system reflect the neutral evolution of mtDNA in populations

Oncogene volume 23, pages 1314–1320 (2004)Cite this article

Abstract

Mitochondrial DNA (mtDNA) instability has been observed in different types of cancer, including colorectal, breast, and gastric cancer. The relationship between the occurrence of such alteration and the nuclear microsatellite instability (nMI) status of the neoplastic cells remains controversial. In an attempt to clarify this issue, we sequenced the first and second mtDNA hypervariable regions, and typed the mitochondrial (CA)n dinucleotide polymorphism in 69 patients with primary tumors of the central nervous system (CNS), previously screened for nMI. Tumor samples showed 27 D-loop sequence changes (39.1%) compared to the corresponding blood samples. Microsatellite homoplasmic allele mutations were detected in four cases (5.8%). We did not find significant associations of the mtDNA instability status with clinicopathological parameters including sex, age, tumor size, and duration of clinical course. Neither did we find any association between mtDNA and nuclear instabilities, indicating that, at least in CNS tumors, they respond to different DNA repair mechanisms. We have also compiled the mtDNA instabilities previously reported by other authors for several types of tumors, comparing them to mtDNA polymorphisms in human populations. Most of the tumor-associated changes are common human polymorphisms and mutational hotspots. To explain the molecular behavior of mtDNA instability in tumors, we propose a model also common to other biological situations.

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Acknowledgements

We are grateful to Patrick Chinnery for helpful comments on an advanced version of this manuscript. We express our appreciation to the sample donors. AS has a research contract with the University of Santiago de Compostela. VM was supported by the Wellcome Trust. This work was supported by grants from the Ministerio de Educación y Ciencia (DGCYT-P4. BIO2000-0145-P4-02), Ministerio de Sanidad (FIS 01/0024), and the Xunta de Galicia (PGIDT-01-PXI-20806-PR and PGIDIT02PXIC20804PN), and Ministerio de Sanidad y Consumo (Fondo de Investigación Sanitaria; Instituto de Salud Carlos III, PI030893; SCO/3425/2002).

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Authors and Affiliations

  1. Unidad de Medicina Molecular, Hospital Clinico Universitario Universidad de Santiago de Compostela, Galicia, Spain

    Ana Vega & Ángel Carracedo

  2. Unidad de Genética Forense, Facultad de Medicina, Universidad de Santiago de Compostela, Galicia, Spain

    Ana Vega, Antonio Salas & Ángel Carracedo

  3. Servicio de Cirugía, Hospital Clínico Universitario de Santiago de Compostela, Galicia, Spain

    Elena Gamborino

  4. Hospital San Rafael, A Coruña, Galicia, Spain

    María Jesús Sobrido

  5. Department of Statistics, University of Oxford, Oxford, UK

    Vincent Macaulay

  6. Department of Statistics, University of Glasgow, Glasgow, UK

    Vincent Macaulay

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  1. Ana Vega
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  2. Antonio Salas
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  3. Elena Gamborino
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  4. María Jesús Sobrido
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  5. Vincent Macaulay
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  6. Ángel Carracedo
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Correspondence to Antonio Salas.

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Vega, A., Salas, A., Gamborino, E. et al. mtDNA mutations in tumors of the central nervous system reflect the neutral evolution of mtDNA in populations. Oncogene 23, 1314–1320 (2004). https://doi.org/10.1038/sj.onc.1207214

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