The landscape of viral associations in human cancers

Zapatka, Marc, Borozan, Ivan, Brewer, Daniel, Iskar, Murat, Grundhoff, Adam, Alawi, Malik, Desai, Nikita, Sültmann, Holger, Moch, Holger, Cooper, Colin, Eils, Roland, Ferretti, Vincent and Lichter, Peter (2020) The landscape of viral associations in human cancers. Nature Genetics, 52 (3). 320–330. ISSN 1061-4036

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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.

Item Type: Article
Uncontrolled Keywords: b-virus integration,cell,genomes,hbv integration,hepatocellular-carcinoma,hpv,human-papillomavirus infection,mutagenesis,mutations,rna-seq data
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 23 Mar 2020 15:19
Last Modified: 30 Jun 2020 00:04
URI: https://ueaeprints.uea.ac.uk/id/eprint/74601
DOI: 10.1038/s41588-019-0558-9

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