The landscape of viral associations in human cancers.
The landscape of viral associations in human cancers.
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DOI：
10.1038/s41588-019-0558-9
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发表时间：
2020-03
期刊：
影响因子：
30.8
通讯作者：
PCAWG Consortium
中科院分区：
文献类型：
--
作者：
Zapatka M;Borozan I;Brewer DS;Iskar M;Grundhoff A;Alawi M;Desai N;Sültmann H;Moch H;PCAWG Pathogens;Cooper CS;Eils R;Ferretti V;Lichter P;PCAWG Consortium
在这里，作为泛癌症全基因组分析（PCAWG）联盟的一部分，我们使用整合了三个独立管道的共识方法系统地研究了潜在的病毒病原体，该联盟汇总了来自38种肿瘤类型的2，658种癌症的全基因组和子集全转录组测序数据。在382个基因组和68个转录组数据集中检测到病毒。我们发现已知的肿瘤相关病毒如EB病毒（EBV）、B肝炎病毒（HBV）和人乳头瘤病毒（HPV;例如，HPV 16或HPV 18）的流行率很高。该研究揭示了HPV和驱动突变在头颈癌中的显着排他性，以及HPV与APOBEC突变特征的关联，这表明抗病毒防御受损是宫颈癌，膀胱癌和头颈癌的驱动力。对于HBV、HPV 16、HPV 18和腺相关病毒-2（AAV 2），病毒整合与基因组拷贝数的局部变异相关。在TERT启动子的整合与高端粒酶表达相关，明显激活了这一肿瘤驱动过程。高水平的内源性逆转录病毒（ERV 1）表达与肾癌患者的生存结局较差有关。癌症基因组中的病毒病原体载量是通过使用多个病原体检测管道分析来自35种癌症类型的2，656个肿瘤的测序数据来估计的，在382个基因组和68个转录组数据集中识别病毒。
Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, for which whole-genome and—for a subset—whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using a consensus approach that integrated three independent pipelines. Viruses were detected in 382 genome and 68 transcriptome datasets. We found a high prevalence of known tumor-associated viruses such as Epstein–Barr virus (EBV), hepatitis B virus (HBV) and human papilloma virus (HPV; for example, HPV16 or HPV18). The study revealed significant exclusivity of HPV and driver mutations in head-and-neck cancer and the association of HPV with APOBEC mutational signatures, which suggests that impaired antiviral defense is a driving force in cervical, bladder and head-and-neck carcinoma. For HBV, HPV16, HPV18 and adeno-associated virus-2 (AAV2), viral integration was associated with local variations in genomic copy numbers. Integrations at the TERT promoter were associated with high telomerase expression evidently activating this tumor-driving process. High levels of endogenous retrovirus (ERV1) expression were linked to a worse survival outcome in patients with kidney cancer. Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.
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