Mitogenomic differences between the normal and tumor cells of colorectal cancer patients

作者：Skonieczna Katarzyna; Malyarchuk Boris; Jawien Arkadiusz; Marszalek Andrzej; Banaszkiewicz Zbigniew; Jarmocik Pawel; Grzybowski Tomasz

来源：Human Mutation, 2018, 39(5): 691-701.

DOI：10.1002/humu.23402

• colon cancer
• haplogroup
• heteroplasmy
• mitochondrial genome
• NGS
• phylogeny

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.

• 出版日期2018-5