MtDNA As a Cancer Marker: A Finally Closed Chapter?

Sequence alterations of the mitochondrial DNA (mtDNA) have been identified in many tu-mor types. Their nature is not entirely clear. Somatic mutation or shifts of heteroplasmic mtDNA vari-ants may play a role. These sequence alterations exhibit a sufficient frequency in all tumor types investi-gated thus far to justify their use as a tumor marker. This statement is supported by the high copy num-ber of mtDNA, which facilitates the detection of aberrant tumor-derived DNA in bodily fluids. This will be of special interest in tumors, which release a relatively high number of cells into bodily fluids, which are easily accessible, most strikingly in urinary bladder carcinoma. Due to the wide distribution of the observed base substitutions, deletions or insertions within the mitochondrial genome, high efforts for whole mtDNA sequencing (16.5 kb) from bodily fluids would be required, if the method would be in-tended for initial tumor screening. However, the usage of mtDNA for sensitive surveillance of known tumor diseases is a meaningful option, which may allow an improved non-invasive follow-up for the urinary bladder carcinoma, as compared to the currently existing cytological or molecular methods. Fol-lowing a short general introduction into mtDNA, this review demonstrates that the scenario of a sensi-tive cancer follow-up by mtDNA-analysis deserves more attention. It would be most important to inves-tigate precisely in the most relevant tumor types, if sequencing approaches in combination with simple PCR-assays for deletions/insertions in homopolymeric tracts has sufficient sensitivity to find most tu-mor-derived mtDNAs in bodily fluids.