Mitochondrial genome instability in cancer

Abstract

The relevant role of mitochondrial mutations in cancer is the most frequent conclusion found in most early publications on the subject. However, it is now clear that this assumption was in many cases based on circumstantial or even flawed evidence. Presently, we know that normal mitochondria structure and functions depend on the concerted interaction between mitochondrial (mt)-genes and different groups of nuclear genes. Thus, somatic mutations of mt- or nuclear genes controlling mitochondrial physiology would influence the cancer transformation process through a disruption of nuclear<-->mitochondrial gene interactions. In this regard, somatic mt-mutations influencing carcinogenesis have been detected in preneoplastic lesions. Furthermore, an abnormal respiration process with the subsequent increase in reactive oxygen species production seems to be one of the basic mechanisms favoring oncogenesis. Many mt-genes exhibit inherited polymorphisms associated with their mitochondrial phylogenetic history. In this report we shall summarize data showing that some of these ethnic mt- mutations may increase or alternatively decrease the susceptibility to various forms of malignancy. The interference of mt-mutations with anticancer therapies and the use of body fluids for the analysis of mt-mutations to obtain tumor samples avoiding invasive techniques are two promising fields to be further investigated.