Mitochondrial Mutagenesis in Cancer

Recent studies have implicated mitochondrial DNA mutations in tumor progression. In this chapter, we provide a review of the studies reporting on mitochondrial DNA mutations and their possible contributions to carcinogenesis. We propose a revised, practical definition for mitochondrial sequence diversity that accounts for observed thresholds found in mutation detection technologies and mitochondrial pathophysiology. Additionally, we describe current and prior efforts to identify somatic mutations in cancer and the challenges unique to mitochondrial DNA mutation analysis. We discuss the mechanisms that may generate these mutations, as well as the spectrum of observed physiological changes in cancer which they produce. Finally, we consider the utility of mitochondrial mutations as a sensitive biomarker in cancer diagnosis, disease prognosis, and patient outcomes.