Clonal expansion of different mtDNA variants without selective advantage in solid tumors

Mutation Research
Julia GekelerRudolf J Wiesner

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.

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Citations

May 13, 2010·The International Journal of Biochemistry & Cell Biology·Katarína SmolkováPetr Ježek
Jun 15, 2010·Environmental and Molecular Mutagenesis·Mariola KulawiecJason H Bielas
May 2, 2013·Head & Neck·Lucio MontebugnoliMaria Pia Foschini
Oct 6, 2010·Virchows Archiv : an International Journal of Pathology·Andrea Ambrosini-SpaltroVincenzo Eusebi
Apr 20, 2018·Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis·Annica HedbergSteinar D Johansen

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