Mitochondrial DNA damage is uncommon in cancer but can promote aggressive behaviour

The mitochondrial genome (mtDNA) has been implicated in carcinogenesis. It is more susceptible than nuclear DNA to damage from reactive oxygen species and mutagens, and has a limited DNA repair machinery. Studies of human cancer have shown that a small proportion of tumours carry significant mtDNA mutations but methodological flaws undermine some of these findings. Mutations in mtDNA are often associated with elevated levels of reactive oxygen species and stabilisation of Hypoxia-Inducible Factor-1 (HIF1), but it has not been clearly demonstrated that these relationships are causal. Some mutations in the coding region of mtDNA can confer increased tumourigenicity, motility and metastasis on cells in vitro and in vivo but these mutations are only rarely found in ex vivo samples. Mitochondrial DNA does not play a major role in common types of cancer, but may promote aggressive behaviour in some cases. Shortcomings in mtDNA repair mechanisms could be exploited to promote apoptosis of tumour cells.