Mitogenomic differences between the normal and tumor cells of colorectal cancer patients |
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| Authors: | Katarzyna Skonieczna Boris Malyarchuk Arkadiusz Jawień Andrzej Marszałek Zbigniew Banaszkiewicz Paweł Jarmocik Tomasz Grzybowski |
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| Affiliation: | 1. Division of Molecular and Forensic Genetics, Department of Forensic Medicine, Faculty of Medicine, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland;2. Institute of Biological Problems of the North, Far‐East Branch of the Russian Academy of Sciences, Magadan, Russia;3. Department of Vascular Surgery and Angiology, Faculty of Medicine, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland;4. Department of Pathology, Faculty of Medicine, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland;5. Department of Tumor Pathology and Prophylaxis, Poznan University of Medical Sciences and Greater Poland Cancer Center, Poznan, Poland |
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| 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. |
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| Keywords: | colon cancer haplogroup heteroplasmy mitochondrial genome NGS phylogeny |
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