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We focus on oncocytic tumors, which are clearly associated with mitochondrial dysfunction. The protein variant pathogenicity was predicted using two computational methods, MutPred and SNPs&amp;GO.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The pathogenicity score of the somatic mtDNA variants were significantly higher in oncocytic tumors compared to non-oncocytic tumors. Variations in subunits of Complex I of the electron transfer chain were significantly more common in tumors with the oncocytic phenotype, while variations in Complex V subunits were significantly more common in non-oncocytic tumors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our results show that the somatic mtDNA mutations reported over all tumors are indistinguishable from a random selection from the set of all possible amino acid variations, and have therefore escaped the effects of purifying selection that act strongly at the population level. We show that the pathogenicity of somatic mtDNA mutations is a determining factor for the oncocytic phenotype. The opposite associations of the Complex I and Complex V variants with the oncocytic and non-oncocytic tumors implies that low mitochondrial membrane potential may play an important role in determining the oncocytic phenotype.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-12-53","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T19:15:11Z","timestamp":1328210111000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Somatic mitochondrial DNA mutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors"],"prefix":"10.1186","volume":"12","author":[{"given":"Lu\u00edsa","family":"Pereira","sequence":"first","affiliation":[]},{"given":"Pedro","family":"Soares","sequence":"additional","affiliation":[]},{"given":"Valdemar","family":"M\u00e1ximo","sequence":"additional","affiliation":[]},{"given":"David C","family":"Samuels","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2012,2,2]]},"reference":[{"issue":"4","key":"3114_CR1","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1086\/502682","volume":"78","author":"DC Samuels","year":"2006","unstructured":"Samuels DC, Carothers AD, Horton R, Chinnery PF: The power to detect disease associations with mitochondrial DNA haplogroups. 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