%0 Journal Article
%T Possibility of selection against mtDNA mutations in tumors
%A M Khaidakov
%A RJ Shmookler Reis
%J Molecular Cancer
%D 2005
%I BioMed Central
%R 10.1186/1476-4598-4-36
%X Accumulation in mutations in mtDNA, leading to an impairment of mitochondrial function, has been implicated in the etiology of aging [1,2] and of several degenerative pathologies including Parkinson's [3], Alzheimer's diseases [4], and diabetes [5]. Similarly, mtDNA mutation is thought to be involved in tumorigenesis based on the presence of novel hetero- and homoplasmies in a number of neoplasms [6]. In the case of degenerative diseases, intracellular clonal expansion of detrimental mtDNA mutations could play a causative role, resulting in cell loss and/or significant functional impairment of affected cells. This logic is not likely to apply to tumorigenesis, and it is not entirely clear at what stage of tumorigenesis a deficiency in aerobic metabolism would confer a selective advantage.Several different scenarios, linking mtDNA mutations to tumorigenesis, can be envisioned. Cells with an elevated mtDNA mutational load may be more susceptible to carcinogenesis due to increased production of ROS by a dysfunctional electron transport chain, which may in turn promote mutagenesis of nuclear genes. On the other hand, cells with relatively intact oxidative phosphorylation would have enhanced prospects for survival. It is also possible that carcinogenesis is influenced to a larger extent by accumulation of mtDNA mutations in organs distal to the tissue of origin, by creating a systemically permissive environment for development of tumors.In a number of studies on mtDNA mutations derived from diverse tumors [7-20], the percentage of samples with clonally expanded mtDNA mutations ranged from 27% to almost 80%, averaging 54 ¡À 5% (mean ¡À SE; see Suppl. Table 1). These findings led investigators to the conclusion that mtDNA mutations are either more common in carcinogenesis, or in some way predispose to it [8,21]. It is not possible, however, to infer the functional importance of mitochondrial DNA mutations to tumorigenesis from these comparisons of tumors to adjacent normal t
%K tumorigenesis
%K mitochondrial DNA
%K mutations
%U http://www.molecular-cancer.com/content/4/1/36