Reznik Ed, Miller Martin L, Şenbabaoğlu Yasin, Riaz Nadeem, Sarungbam Judy, Tickoo Satish K, Al-Ahmadie Hikmat A, Lee William, Seshan Venkatraman E, Hakimi A Ari, Sander Chris
Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.
Cancer Research UK, Cambridge Institute, Cambridge, United Kingdom.
Elife. 2016 Feb 22;5:e10769. doi: 10.7554/eLife.10769.
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.
线粒体DNA（mtDNA）的突变、缺失及拷贝数变化在各类癌症中均有发现。在此，我们调查了癌症基因组图谱计划所分析的22种肿瘤类型中的mtDNA拷贝数变异情况。我们发现，相对于匹配的正常组织，某些癌症，尤其是膀胱癌、乳腺癌和肾癌，存在mtDNA缺失的倾向。对遗传背景的分析揭示了包括胶质瘤中异柠檬酸脱氢酶1（IDH1）突变在内的几种体细胞改变的发生率与mtDNA含量之间的关联。在部分而非所有癌症类型中，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呈负相关。结合免疫组化证据，我们发现一些肿瘤可能通过补偿mtDNA缺失来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。
