Tumor-specific changes in mtDNA content in human cancer

Authors

  • Elizabeth Mambo,

    1. Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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    • The first two authors contributed equally to this paper.

  • Aditi Chatterjee,

    1. Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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    • The first two authors contributed equally to this paper.

  • Mingzhao Xing,

    1. Division of Endocrinology and Metabolism, Department of Medicine, The Johns Hopkins University, School of Medicine, Baltimore, MD, USA
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  • Giovanni Tallini,

    1. Department of Pathology, University of Bologna School of Medicine, Bologna, Italy
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  • Bryan R. Haugen,

    1. Department of Medicine, University of Colorado Health Sciences Center, Aurora, CO, USA
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  • Sai-Ching J. Yeung,

    1. Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
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  • Saraswati Sukumar,

    1. Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, School of Medicine, Baltimore, MD, USA
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  • David Sidransky

    Corresponding author
    1. Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, 720 Rutland Avenue, Johns Hopkins University School of Medicine, 818 Ross Research Building, Baltimore, MD 21205-2196
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    • Fax: +410-614-1411.


Abstract

Mitochondrial DNA (mtDNA) alterations are associated with various cancer types, suggesting that the mitochondrial genome may be a critical contributing factor in carcinogenesis. mtDNA alterations have been suggested as a potentially sensitive and specific biomarker for several cancer types. We examined mtDNA content in 25 pairs of normal and tumor breast tissue samples, 37 papillary thyroid carcinoma (PTC), 21 benign thyroid neoplasms and in 20 paired normal and PTC samples. Our results showed that mtDNA content was reduced in 80% of the breast tumors relative to their corresponding normal. mtDNA was increased in papillary thyroid carcinomas, however, when compared to the corresponding normal DNA taken from the same individual. Also, mtDNA content was increased in none-paired PTC samples compared to the normal controls. Our findings indicate that changes in mtDNA content during carcinogenesis may be regulated in a tumor specific manner. Additionally, changes in mtDNA levels did not correlate with tumor grade and metastasis, suggesting that these alterations may occur in the early stages of tumorigenesis. Our findings suggest that mtDNA content can be used as a molecular diagnostic tool to help identify genetic abnormalities in human tumors. © 2005 Wiley-Liss, Inc.

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