Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types.
Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types.
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DOI：
10.1016/j.celrep.2018.03.047
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发表时间：
2018-04-03
期刊：
影响因子：
8.8
通讯作者：
Liang H
中科院分区：
文献类型：
--
作者：
Ge Z;Leighton JS;Wang Y;Peng X;Chen Z;Chen H;Sun Y;Yao F;Li J;Zhang H;Liu J;Shriver CD;Hu H;Cancer Genome Atlas Research Network;Piwnica-Worms H;Ma L;Liang H
蛋白质泛素化是将单个泛素分子或各种泛素链添加到靶蛋白上的动态可逆过程。在这里，使用来自癌症基因组图谱的33种癌症类型的9，125个肿瘤样本的多维组学数据，我们对929个泛素相关基因和95个去泛素化酶基因进行了全面的分子表征。其中，我们系统地识别了顶级体细胞驱动因子候选者，包括具有癌症类型特异性模式的突变FBXW 7和与BRAF突变显示互斥模式的扩增MDM 2。泛素途径基因在多种机制介导的癌症中倾向于上调。通过整合泛癌症多组学数据，我们确定了一组表现出更差预后的肿瘤样本。这些样品始终与细胞周期和DNA修复途径的上调相关，其特征在于突变的TP 53、MYC/TERT扩增和APC/PTEN缺失。我们的分析强调了泛素途径在癌症发展中的重要性，并为制定相关的治疗策略奠定了基础。Ge等人分析了33种癌症类型的9，125个TCGA样本的队列，以提供泛素途径的全面表征。他们检测了泛素途径中的体细胞驱动候选者，并确定了一组生存率差的患者，突出了这一途径在癌症发展中的重要性。
Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies. Ge et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to provide a comprehensive characterization of the ubiquitin pathway. They detect somatic driver candidates in the ubiquitin pathway and identify a cluster of patients with poor survival, highlighting the importance of this pathway in cancer development.
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