The landscape of viral associations in human cancers

Nat Genet. 2020 Mar;52(3):320-330. doi: 10.1038/s41588-019-0558-9. Epub 2020 Feb 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Copy Number Variations
  • DNA Tumor Viruses / genetics*
  • Genome, Human / genetics*
  • Hepatitis B virus / genetics
  • Herpesvirus 4, Human / genetics
  • Humans
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / virology*
  • Papillomavirus Infections / genetics
  • Promoter Regions, Genetic / genetics
  • Telomerase / genetics
  • Transcriptome*
  • Tumor Virus Infections / virology*
  • Virus Integration*

Substances

  • TERT protein, human
  • Telomerase