文章：

线粒体DNA变异与癌症

Mitochondrial DNA variation and cancer

原文发布日期：2021-05-27

DOI: 10.1038/s41568-021-00358-w

类型: Review Article

开放获取: 否

英文摘要：

Variation in the mitochondrial DNA (mtDNA) sequence is common in certain tumours. Two classes of cancer mtDNA variants can be identified: de novo mutations that act as ‘inducers’ of carcinogenesis and functional variants that act as ‘adaptors’, permitting cancer cells to thrive in different environments. These mtDNA variants have three origins: inherited variants, which run in families, somatic mutations arising within each cell or individual, and variants that are also associated with ancient mtDNA lineages (haplogroups) and are thought to permit adaptation to changing tissue or geographic environments. In addition to mtDNA sequence variation, mtDNA copy number and perhaps transfer of mtDNA sequences into the nucleus can contribute to certain cancers. Strong functional relevance of mtDNA variation has been demonstrated in oncocytoma and prostate cancer, while mtDNA variation has been reported in multiple other cancer types. Alterations in nuclear DNA-encoded mitochondrial genes have confirmed the importance of mitochondrial metabolism in cancer, affecting mitochondrial reactive oxygen species production, redox state and mitochondrial intermediates that act as substrates for chromatin-modifying enzymes. Hence, subtle changes in the mitochondrial genotype can have profound effects on the nucleus, as well as carcinogenesis and cancer progression.

摘要翻译： 

线粒体DNA（mtDNA）序列变异在特定肿瘤中较为常见。癌症相关的mtDNA变异可分为两类：作为致癌“诱导因子”的新生突变，以及作为“适应因子”使癌细胞在不同环境中得以存续的功能性变异。这些mtDNA变异具有三种来源：家族遗传的种系变异、个体细胞内产生的体细胞突变，以及与古老mtDNA谱系（单倍群）相关的适应性变异——这些变异被认为能促进细胞适应变化的组织或地理环境。除mtDNA序列变异外，mtDNA拷贝数变化及mtDNA序列向核内的转移也可能参与某些癌症的发生。mtDNA变异在嗜酸细胞瘤和前列腺癌中已证实具有显著功能相关性，同时在多种其他癌症类型中也有报道。核DNA编码的线粒体基因改变进一步证实了线粒体代谢在癌症中的重要性，包括影响线粒体活性氧生成、氧化还原状态，以及作为染色质修饰酶底物的线粒体中间产物。因此，线粒体基因型的细微改变可能对细胞核、癌变过程及癌症进展产生深远影响。

原文链接：

Mitochondrial DNA variation and cancer