Journal
LIFE SCIENCES
Volume 89, Issue 3-4, Pages 65-71Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2011.05.010
Keywords
Mitochondrial DNA; Copy number; Cancer; Biomarkers
Funding
- Canadian Institutes of Health Research (CIHR)
- University of Ottawa, Tianjin Municipal Science and Technology Commission, China
- Chinese government
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Mitochondria are key organelles in eukaryotic cells principally responsible for multiple cellular functions. In addition to a plethora of somatic mutations as well as polymorphic sequence variations in mitochondrial DNA (mtDNA), the identification of increased or reduced mtDNA copy number has been increasingly reported in a broad range of primary human cancers, underscoring that accumulation of mtDNA content alterations may be a pivotal factor in eliciting persistent mitochondrial deficient activities and eventually contributing to cancer pathogenesis and progression. However, the detailed roles of altered mtDNA amount in driving the tumorigenic process remain largely unknown. This review outlines mtDNA content changes present in various types of common human malignancies and briefly describes the possible causes and their potential connections to the carcinogenic process. The present state of our knowledge regarding how altered mtDNA quantitative levels could be utilized as a diagnostic biomarker for identifying genetically predisposed population that should undergo intensive screening and early surveillance program is also discussed. Taken together, these findings strongly indicate that mtDNA copy number alterations may exert a crucial role in the pathogenic mechanisms of tumor development. Continued insights into the functional significance of altered mtDNA quantities in the etiology of human cancers will hopefully help in establishing novel potential targets for anti-tumor drugs and intervention therapies. (C) 2011 Elsevier Inc. All rights reserved.
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