Mitochondria are essential cellular organelles that play critical roles in cancer. Here, as part of the International Cancer Genome Consortium/The Cancer Genome Atlas Pan-Cancer Analysis of Whole Genomes Consortium, which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we performed a multidimensional, integrated characterization of mitochondrial genomes and related RNA sequencing data. Our analysis presents the most definitive mutational landscape of mitochondrial genomes and identifies several hypermutated cases. Truncating mutations are markedly enriched in kidney, colorectal and thyroid cancers, suggesting oncogenic effects with the activation of signaling pathways. We find frequent somatic nuclear transfers of mitochondrial DNA, some of which disrupt therapeutic target genes. Mitochondrial copy number varies greatly within and across cancers and correlates with clinical variables. Co-expression analysis highlights the function of mitochondrial genes in oxidative phosphorylation, DNA repair and the cell cycle, and shows their connections with clinically actionable genes. Our study lays a foundation for translating mitochondrial biology into clinical applications.

中文翻译：

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人类癌症中线粒体基因组的综合分子特征。

线粒体是在癌症中发挥关键作用的重要细胞器。在这里，作为国际癌症基因组联盟/全基因组联盟的癌症基因组图谱泛癌症分析的一部分，该联盟汇集了来自 38 种肿瘤类型的 2,658 种癌症的全基因组测序数据，我们对线粒体基因组和相关的 RNA 测序数据。我们的分析展示了线粒体基因组最明确的突变景观，并确定了几个超突变案例。截短突变在肾癌、结直肠癌和甲状腺癌中显着增多，表明信号通路的激活具有致癌作用。我们发现线粒体 DNA 的频繁体细胞核转移，其中一些破坏了治疗靶基因。线粒体拷贝数在癌症内部和癌症之间变化很大，并与临床变量相关。共表达分析突出了线粒体基因在氧化磷酸化、DNA 修复和细胞周期中的功能，并显示了它们与临床可操作基因的联系。我们的研究为将线粒体生物学转化为临床应用奠定了基础。