Mitochondrial DNA copy number variation across human cancers
Mitochondrial DNA copy number variation across human cancers
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DOI：
10.7554/elife.10769
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发表时间：
2016-02-22
期刊：
影响因子：
7.7
通讯作者：
Sander, Chris
中科院分区：
文献类型：
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作者：
Reznik, Ed;Miller, Martin L.;Sander, Chris
线粒体DNA （mtDNA）拷贝数的突变、缺失和变化在癌症中都可以观察到。在这里，我们调查了癌症基因组图谱项目描述的22种肿瘤类型的mtDNA拷贝数变化。我们观察到一些癌症，特别是膀胱癌、乳腺癌和肾癌，相对于匹配的正常组织，mtDNA有减少的趋势。遗传背景分析揭示了几种体细胞改变的发生率，包括胶质瘤中IDH1突变和mtDNA含量之间的关联。在一些但不是所有的癌症类型中，mtDNA含量与呼吸基因的表达相关，而与免疫反应和细胞周期基因的表达反相关。结合免疫组织化学证据，我们发现一些肿瘤可能补偿mtDNA的消耗以维持呼吸蛋白的水平。我们的结果突出了肿瘤中mtDNA拷贝数变异的程度，并指出了相关的治疗机会。
Mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), are observed throughout cancers. Here, we survey mtDNA copy number variation across 22 tumor types profiled by The Cancer Genome Atlas project. We observe a tendency for some cancers, especially of the bladder, breast, and kidney, to be depleted of mtDNA, relative to matched normal tissue. Analysis of genetic context reveals an association between incidence of several somatic alterations, including IDH1 mutations in gliomas, and mtDNA content. In some but not all cancer types, mtDNA content is correlated with the expression of respiratory genes, and anti correlated to the expression of immune response and cell-cycle genes. In tandem with immunohistochemical evidence, we find that some tumors may compensate for mtDNA depletion to sustain levels of respiratory proteins. Our results highlight the extent of mtDNA copy number variation in tumors and point to related therapeutic opportunities.