The landscape of viral associations in human cancers
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Open Access
- 5 February 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 52 (3), 320-330
- https://doi.org/10.1038/s41588-019-0558-9
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.Keywords
Funding Information
- Bundesministerium für Bildung und Forschung (01EK1502C, 01KU1505A-G, 01EK1502C, 01KU1505A-G)
- Ontario Institute for Cancer Research
- Cancer Research UK (C5047/A14835/A22530/A17528, C5047/A14835/A22530/A17528)
- Dallaglio Foundation, Bob Champion Cancer Trust, The Masonic Charitable Foundation, The King Family, Stephen Hargrave Trust
- Leibniz Association | Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie – Hans-Knöll-Institut (SAW-2015-IPB-2)
- Deutsches Zentrum für Infektionsforschung (TTU 01.801)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (S-87701-03-01)
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