Mitogenomic differences between the normal and tumor cells of colorectal cancer patients. Issue 5 (24th January 2018)

• Record Type: Journal Article
• Authors: Skonieczna, Katarzyna; Malyarchuk, Boris; Jawień, Arkadiusz; Marszałek, Andrzej; Banaszkiewicz, Zbigniew; Jarmocik, Paweł; Grzybowski, Tomasz
• Is Part Of: Human mutation. Volume 39:Issue 5(2018)
• Page Start: 691
• Page End: 701
• Publication Date: 2018-01-24
• Subjects: colon cancer -- haplogroup -- heteroplasmy -- mitochondrial genome -- NGS -- phylogeny; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.23402
• Languages: English
• ISSNs: 1059-7794

Abstract

Abstract: So far, a reliable spectrum of mitochondrial DNA mutations in colorectal cancer cells is still unknown, and neither is their significance in carcinogenesis. Indeed, it remains debatable whether mtDNA mutations are "drivers" or "passengers" of colorectal carcinogenesis. Thus, we analyzed 200 mitogenomes from normal and cancer tissues of 100 colorectal cancer patients. Minority variant mutations were detected at the 1% level. We showed that somatic mutations frequently occur in colorectal cancer cells (75%) and are randomly distributed across the mitochondrial genome. Mutational signatures of somatic mitogenome mutations suggest that they might arise through nucleotide deamination due to oxidative stress. The majority of somatic mutations localized within the coding region (in positions not known from the human phylogeny) and was potentially pathogenic to cell metabolism. Further analysis suggested that the relaxation of negative selection in the mitogenomes of colorectal cancer cells may allow accumulation of somatic mutations. Thus, a shift in glucose metabolism from oxidative phosphorylation to glycolysis may create advantageous conditions for accumulation of mtDNA mutations. Considering the fact that the presence of somatic mtDNA mutations was not associated with any clinicopathological features, we suggested that mtDNA somatic mutations are "passengers" rather than the cause of colorectal carcinogenesis. Abstract : Somatic mutations frequently occur and are randomly distributed across colorectal cancer mitogenomes. These somatic mutations accumulated in mitochondrial genomes possibly due to the relaxation of negative selection in colorectal cancer cells. Together with the observation that the presence of somatic mitogenome mutations was not associated with any clinicopathological features of colorectal cancer patients, we suggested that somatic mtDNA mutations are passengers rather than the cause of colorectal carcinogenesis.