人癌症中病毒的分布
2020-02-11   阅读:384   来源:自然

德国癌症研究中心Peter Lichter研究团队近日取得一项新成果。他们的最新研究探索了人类癌症中病毒的分布。2020年2月5日,国际学术期刊《自然—遗传学》在线发表了这一成果。

作为泛癌全基因组分析(PCAWG)联和会的一部分,该数据库收集了38个肿瘤类型的2,658例癌症样本的全基因组和一部分转录全基因组测序数据,研究人员利用共识的方法整合了三个独立数据库用以系统地研究潜在的病毒病原体。在382个基因组和68个转录组数据集中都检测到了病毒存在。研究发现,已知的与肿瘤相关的病毒(如爱泼斯坦-巴尔病毒(EBV),乙型肝炎病毒(HBV)和人乳头瘤病毒(HPV;例如HPV16或HPV18))的检出率都很高。这项研究揭示了头颈癌中HPV和驱动基因突变的显着排它性以及HPV与APOBEC突变特征的相关性,这表明抗病毒防御能力下降是宫颈癌、膀胱癌和头颈癌的诱因。对于HBV、HPV16、HPV18和腺相关病毒2(AAV2),病毒整合与基因组拷贝数的局部变化有关。在TERT启动子处的整合与端粒酶的高表达有关,从而明显激活了该肿瘤的发育过程。内源性逆转录病毒(ERV1)的高表达与肾癌患者较差的生存期有关。

附:英文原文

Title: The landscape of viral associations in human cancers

Author: Marc Zapatka, Ivan Borozan, Daniel S. Brewer, Murat Iskar, Adam Grundhoff, Malik Alawi, Nikita Desai, Holger Sltmann, Holger Moch, Colin S. Cooper, Roland Eils, Vincent Ferretti, Peter Lichter

Issue&Volume: 2020-02-05

Abstract: 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.

DOI: 10.1038/s41588-019-0558-9

编辑:小柯机器人

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