The landscape of viral associations in human cancers

• Published in: Nature genetics Vol. 52; no. 3; pp. 320 - 330
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2020; Nature Publishing Group
• Subjects: 38; 38/23; 38/91; 45; 631/67; 692/699/67; Agriculture; Animal Genetics and Genomics; 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; 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; Medicin och hälsovetenskap; Medicinsk genetik; 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
• DOI: 10.1038/s41588-019-0558-9

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.