The landscape of viral associations in human cancers

Abstract

Potential viral pathogens were systematically investigated in the whole-genome and transcriptome sequencing of 2,656 donors as part of the Pan-Cancer Analysis of Whole Genomes using a consensus approach integrating three independent pathogen detection pipelines. Viruses were detected in 382 genomic and 68 transcriptome data sets. We extensively searched and characterized numerous features of virus-positive cancers integrating various PCAWG datasets. We show the high prevalence of known tumor associated viruses such as EBV, HBV and several HPV types. Our systematic analysis revealed that HPV presence was significantly exclusive with well-known driver mutations in head/neck cancer. A strong association was observed between HPV infection and the APOBEC mutational signatures, suggesting the role of impaired mechanism of antiviral cellular defense as a driving force in the development of cervical, bladder and head neck carcinoma. Viral integration into the host genome was observed for HBV, HPV16, HPV18 and AAV2 and associated with a local increase in copy number variations. The recurrent viral integrations at the TERT promoter were coupled to high telomerase expression uncovering a further mechanism to activate this tumor driving process. High levels of endogenous retrovirus ERV1 expression is linked to worse survival outcome in kidney cancer.

An atlas of the tissue and blood metagenome in cancer reveals novel links between bacteria, viruses and cancer

“…Out of these, 27 taxa remained being likely cancer-associated after extensive filtering. While studies on the viral metagenome of caner tissues and patients have been performed using datasets from cancer genomics studies 4,5,21,22 , similar large studies looking at the bacterial metagenome are lacking.…”

“…Studies examining the viral metagenome of cancer tissues mainly identified known associations of Human Papillomavirus with cervical and head and neck cancer, Hepatitis B in liver cancer and Human Herpesvirus 5 in a variety of cancers while detection of Human Mastadenovirus C was controversial 4,5,21,22 .…”

“…While the immunosuppression associated with hematological cancers and subsequent treatment obviously predisposes to infections with unusual pathogens from the environment, it is at least possible that these patients had a latent infection with Gordonia polyisoprenivorans which exacerbated into bacteremia and sepsis upon treatment-induced immunosuppression. Human Mastadenovirus C has to date not been clearly linked to cancer, though two recent reports have found it frequently in various cancer tissue, with one treating it as contamination 4 and one not 21 response, which has been described as being an important pathomechanism of CLL 41 . In addition to CLL patients, both Gordonia polyisoprenivorans and Human Mastadenovirus C were also detected frequently in other cancers, sometimes at high levels, while never being detected in healthy donors.…”

“…Resulting datasets contain traces of non-human, or, more general, non-host origin that is present either because of genomic integration or presence of the virus or bacteria in the tissue itself. While some studies have already been performed with the goal to repurpose this data to unravel novel associations between infections and cancer 4,5,[20][21][22] , these resources have so far been underutilized to discover novel, possible associations between cancers and infections.…”

VIRTUS: a pipeline for comprehensive virus analysis from conventional RNA-seq data

“…A variety of virus species including retroviruses, flaviviruses and herpesviruses, might contribute to the development of human diseases including autoimmune diseases and cancers. For example, Epstein-Barr virus (EBV) has been reported to play a causative role for head-neck cancer and lymphoma (Zapatka et al, 2020), and possibly for multiple sclerosis and systemic lupus erythematosus (Harley et al, 2018). It remains to be determined, however, which viruses are present in normal tissues and whether their state of activation contributes to disease development.…”