The landscape of viral associations in human cancers

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)320–330
Number of pages11
JournalNature Genetics
Volume52
Issue number3
Early online date5 Feb 2020
DOIs
Publication statusPublished - Mar 2020

Keywords

  • B-VIRUS INTEGRATION
  • CELL
  • GENOMES
  • HBV INTEGRATION
  • HEPATOCELLULAR-CARCINOMA
  • HPV
  • HUMAN-PAPILLOMAVIRUS INFECTION
  • MUTAGENESIS
  • MUTATIONS
  • RNA-SEQ DATA

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