Abstract
The study of somatic DNA instabilities constitutes a debatable topic because different causes can lead to seeming DNA alteration patterns between different cells or tissues from the same individual. Carcinogenesis or the action of a particular toxic could generate such patterns, and this is in fact the leitmotif of a number of studies on mitochondrial DNA (mtDNA) instability. Patterns of seeming instabilities could also arise from technical errors at any stage of the analysis (DNA extraction, amplification, mutation screening/sequencing, and documentation). Specifically, inadvertent DNA contamination or sample mixing would yield mosaic variation that could be erroneously interpreted as real mutation differences (instabilities) between tissues from the same individual. From the very beginning, mtDNA studies comparing cancerous to non-cancerous tissues have suffered from such mosaic results. We demonstrate here that the phylogenetic linkage of whole arrays of mtDNA mutations provides strong evidence of artificial recombination in previous studies on buccal cells and oral squamous cell carcinoma.
Highlights
Mitochondrial DNA analysis of different tissues and cells from an individual is often carried out in order to learn more about the distribution of some minor variation of mitochondrial DNA (mtDNA) molecules within an organism and about spontaneous somatic mutations that could play a role in carcinogenesis, in particular
Oral squamous cell carcinoma Prior et al [11] extracted mtDNA from 30 paired samples of tumour and non-tumour tissue, which was analyzed for contrasting variation within the two short fragments 4527–4954 and 30–407
Neither of the two studies published in the journal Carcinogenesis which we have reassessed here can provide any convincing indication of an increased amount of somatic point mutations in smokers or cancerous tissues, since the reported variation shows the typical imprint of mosaicism of amplicons caused by inadvertent contamination and sample confusion
Summary
Mitochondrial DNA analysis of different tissues and cells from an individual is often carried out in order to learn more about the distribution of some minor variation (heteroplasmy) of mtDNA molecules within an organism and about spontaneous somatic mutations that could play a role in carcinogenesis, in particular Such analysis is, more often than generally believed, beset with problems related to the quality of mtDNA samples, DNA extraction, PCR and sequencing protocols, and the omnipresent risk of contamination and documentation errors [1,2,3,4,5,6,7,8]. This allows the researcher who has the necessary knowledge about natural mtDNA variation to question mtDNA sequencing results
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