title: Clonal expansion of different mtDNA variants without selective advantage in solid tumors.
abstract: In search of tumor-specific mitochondrial DNA (mtDNA) mutations in head and neck squamous cell cancer, we found heteroplasmy in the blood of two individuals, i.e., these individuals carried two alleles of mtDNA. In both cases, the tumor was found to be homoplasmic, i.e., it contained only one of the two mtDNA alleles present in blood. More interestingly, in one case the tumor had acquired the wild-type allele, while in the other case it contained the mutant allele only. Sequencing of the whole 16.5 kb mtDNA showed that the observed heteroplasmic positions in the D-loop region, nucleotides 152 and 16187, respectively, were the only differences between tumor and blood mtDNA genotypes in these individuals. Our findings thus strongly support the hypothesis that accumulation of mtDNA mutations in solid tumors occurs by clonal and random expansion of pre-existing alleles and is not necessary for the metabolic changes generally associated with tumor formation, the Warburg effect.
authors.affiliation: Institute of Vegetative Physiology, Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, University of Köln, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Gekeler
authors.forename: Gábor
authors.initials: G
authors.lastname: Zsurka
authors.forename: Wolfram S
authors.initials: WS
authors.lastname: Kunz
authors.forename: Simon F
authors.initials: SF
authors.lastname: Preuss
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Klussmann
authors.forename: Orlando
authors.initials: O
authors.lastname: Guntinas-Lichius
authors.forename: Rudolf J
authors.initials: RJ
authors.lastname: Wiesner
mesh_terms: D000368:Aged; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: D004272:DNA, Mitochondrial