The landscape of viral associations in human cancers

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...

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Vydáno v:	Nature genetics Ročník 52; číslo 3; s. 320 - 330
Hlavní autoři:	Zapatka, Marc, Borozan, Ivan, Brewer, Daniel S., Iskar, Murat, Grundhoff, Adam, Alawi, Malik, Desai, Nikita, Sültmann, Holger, Moch, Holger, Cooper, Colin S., Eils, Roland, Ferretti, Vincent, Lichter, Peter
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.03.2020 Nature Publishing Group
Témata:	38 38/23 38/91 45 631/67 692/699/67 Agriculture Animal Genetics and Genomics Antiviral drugs Basic Medicine Biomedical and Life Sciences Biomedicine Bladder Cancer Cancer Research Causes of Consortia Cytomegalovirus Datasets Deoxyribonucleic acid Development and progression DNA DNA Copy Number Variations DNA Tumor Viruses - genetics Endogenous retroviruses Epstein-Barr virus Gene expression Gene Function Genetic aspects Genome, Human - genetics Genomes Head & neck cancer Health aspects Hepatitis Hepatitis B Hepatitis B virus - genetics Herpesvirus 4, Human - genetics Human Genetics Human papillomavirus Humans Infections Kidney cancer Medical and Health Sciences Medical Genetics and Genomics (including Gene Therapy) Medicin och hälsovetenskap Medicinsk genetik och genomik (Här ingår: Genterapi) Medicinska och farmaceutiska grundvetenskaper Mutation Neoplasms - genetics Neoplasms - virology Papillomavirus Infections - genetics Pathogens Promoter Regions, Genetic - genetics Telomerase Telomerase - genetics Transcriptome Tumor Virus Infections - virology Tumors Virus Integration Viruses United Kingdom
ISSN:	1061-4036, 1546-1718, 1546-1718
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/s41588-019-0558-9