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首页> 外文期刊>Mitochondrion >Heteroplasmic mutation of mitochondrial DNA D-loop and 4977-bp deletion in human cancer cells during mitochondrial DNA depletion
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Heteroplasmic mutation of mitochondrial DNA D-loop and 4977-bp deletion in human cancer cells during mitochondrial DNA depletion

机译:线粒体DNA耗竭过程中人类癌细胞线粒体DNA D环的异质突变和4977-bp缺失

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摘要

Somatic mutations in mitochondrial DNA (mtDNA) have been demonstrated in various human cancers. Many cancers have high frequently of mtDNA with homoplasmic point mutations, and carry less frequently of mtDNA with large-scale deletions as compared with corresponding non-cancerous tissue. Moreover, most cancers harbor a decreased copy number of mtDNA than their corresponding non-cancerous tissue. However, it is unclear whether the process of decreasing in mtDNA content would be involved in an increase in the heteroplasmic level of somatic mtDNA point mutation, and/or involved in a decrease in the proportion of mtDNA with large-scale deletion in cancer cells. In this study, we provided evidence that the heteroplasmic levels of variations in cytidine number in np 303-309 poly C tract of mtDNA in three colon cancer cells were not changed during an ethidium bromide-induced mtDNA depleting process. In the mtDNA depleting process, the proportions of mtDNA with 4977-bp deletion in cybrid cells were not significantly altered. These results suggest that the decreasing process of mtDNA copy number per se may neither contribute to the shift of homoplasmic/heteroplasmic state of point mutation in mtDNA nor to the decrease in proportion of mtDNA with large-scale deletions in cancer cells. Mitochondrial genome instability and reduced mtDNA copy number may independently occur in human cancer.
机译:线粒体DNA(mtDNA)中的体细胞突变已在各种人类癌症中得到证实。与相应的非癌组织相比,许多癌症具有同质点突变的mtDNA的发生频率较高,而带有大规模缺失的mtDNA的发生频率较低。此外,与相应的非癌组织相比,大多数癌症的mtDNA拷贝数减少。然而,尚不清楚降低mtDNA含量的过程是否会导致体细胞mtDNA点突变的异质水平提高,和/或是否会导致癌细胞中大规模缺失的mtDNA比例降低。在这项研究中,我们提供了证据,表明在三个溴化乙锭诱导的mtDNA消耗过程中,三个结肠癌细胞中mtDNA的np 303-309多C道胞苷值的异质水平没有变化。在mtDNA耗竭过程中,杂种细胞中缺失4977 bp的mtDNA的比例没有明显改变。这些结果表明,mtDNA拷贝数的降低过程本身可能既不会导致mtDNA中点突变的同质/异质状态的改变,也不会导致癌细胞中大规模缺失的mtDNA比例的降低。线粒体基因组不稳定性和降低的mtDNA拷贝数可能在人类癌症中独立发生。

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