title: Comprehensive metagenomic analysis of glioblastoma reveals absence of known virus despite antiviral-like type I interferon gene response.
abstract: Glioblastoma is a deadly malignant brain tumor and one of the most incurable forms of cancer in need of new therapeutic targets. As some cancers are known to be caused by a virus, the discovery of viruses could open the possibility to treat, and perhaps prevent, such a disease. Although an association with viruses such as cytomegalovirus or Simian virus 40 has been strongly suggested, involvement of these and other viruses in the initiation and/or propagation of glioblastoma remains vague, controversial and warrants elucidation. To exhaustively address the association of virus and glioblastoma, we developed and validated a robust metagenomic approach to analyze patient biopsies via high-throughput sequencing, a sensitive tool for virus screening. In addition to traditional clinical diagnostics, glioblastoma biopsies were deep-sequenced and analyzed with a multistage computational pipeline to identify known or potentially discover unknown viruses. In contrast to the studies reporting the presence of viral signatures in glioblastoma, no common or recurring active viruses were detected, despite finding an antiviral-like type I interferon response in some specimens. Our findings highlight a discrete and non-specific viral signature and uncharacterized short RNA sequences in glioblastoma. This study provides new insights into glioblastoma pathogenesis and defines a general methodology that can be used for high-resolution virus screening and discovery in human cancers.
authors.affiliation: Laboratory of Immunohematology, Hematology Unit, Department of Genetic and Laboratory Medicine, Geneva University Hospitals, University of Geneva, Switzerland.
authors.forename: Érika
authors.initials: É
authors.lastname: Cosset
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Petty
authors.forename: Valérie
authors.initials: V
authors.lastname: Dutoit
authors.forename: Samuel
authors.initials: S
authors.lastname: Cordey
authors.forename: Ismael
authors.initials: I
authors.lastname: Padioleau
authors.forename: Patricia
authors.initials: P
authors.lastname: Otten-Hernandez
authors.forename: Laurent
authors.initials: L
authors.lastname: Farinelli
authors.forename: Laurent
authors.initials: L
authors.lastname: Kaiser
authors.forename: Pascale
authors.initials: P
authors.lastname: Bruyère-Cerdan
authors.forename: Diderik
authors.initials: D
authors.lastname: Tirefort
authors.forename: Soraya
authors.initials: S
authors.lastname: Amar El-Dusouqui
authors.forename: Zeynab
authors.initials: Z
authors.lastname: Nayernia
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Krause
authors.forename: Evgeny M
authors.initials: EM
authors.lastname: Zdobnov
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Dietrich
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Rigal
authors.forename: Olivier
authors.initials: O
authors.lastname: Preynat-Seauve
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D003587:Cytomegalovirus / Q000276:immunology*; D005909:Glioblastoma / Q000235:genetics* / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007370:Interferon Type I / Q000276:immunology*; D056186:Metagenomics
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007370:Interferon Type I
keywords: antiviral type I interferon response; glioblastoma multiforme; high-throughput sequencing; metagenomic analysis; virus discovery