Oncogene (2006) 25, 4663–4674. doi:10.1038/sj.onc.1209604

Mitochondrial DNA mutations in human cancer

A Chatterjee1, E Mambo1 and D Sidransky1

1Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Correspondence: Dr D Sidransky, 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, USA. E-mail:



Somatic mitochondrial DNA (mtDNA) mutations have been increasingly observed in primary human cancers. As each cell contains many mitochondria with multiple copies of mtDNA, it is possible that wild-type and mutant mtDNA can co-exist in a state called heteroplasmy. During cell division, mitochondria are randomly distributed to daughter cells. Over time, the proportion of the mutant mtDNA within the cell can vary and may drift toward predominantly mutant or wild type to achieve homoplasmy. Thus, the biological impact of a given mutation may vary, depending on the proportion of mutant mtDNAs carried by the cell. This effect contributes to the various phenotypes observed among family members carrying the same pathogenic mtDNA mutation. Most mutations occur in the coding sequences but few result in substantial amino acid changes raising questions as to their biological consequence. Studies reveal that mtDNA play a crucial role in the development of cancer but further work is required to establish the functional significance of specific mitochondrial mutations in cancer and disease progression. The origin of somatic mtDNA mutations in human cancer and their potential diagnostic and therapeutic implications in cancer are discussed. This review article provides a detailed summary of mtDNA mutations that have been reported in various types of cancer. Furthermore, this review offers some perspective as to the origin of these of mutations, their functional consequences in cancer development, and possible therapeutic implications.


mitochondria, mutation, homoplasmy, reactive oxygen species (ROS), molecular detection