Comprehensive metagenomic analysis of glioblastoma reveals absence of known virus despite antiviral‐like type I interferon gene response

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 associati...

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Veröffentlicht in:	International journal of cancer Jg. 135; H. 6; S. 1381 - 1389
Hauptverfasser:	Cosset, Érika, Petty, Tom J., Dutoit, Valérie, Cordey, Samuel, Padioleau, Ismael, Otten‐Hernandez, Patricia, Farinelli, Laurent, Kaiser, Laurent, Bruyère‐Cerdan, Pascale, Tirefort, Diderik, Amar El‐Dusouqui, Soraya, Nayernia, Zeynab, Krause, Karl‐Heinz, Zdobnov, Evgeny M., Dietrich, Pierre‐Yves, Rigal, Emmanuel, Preynat‐Seauve, Olivier
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Hoboken, NJ Wiley-Blackwell 15.09.2014 Wiley Subscription Services, Inc Wiley BlackWell Publishing Ltd
Schlagworte:	Antibodies, Viral - blood Antiviral drugs antiviral type I interferon response Biological and medical sciences Biopsy Brain cancer Brain Neoplasms - genetics Brain Neoplasms - immunology Brain Neoplasms - virology Brain tumors Cancer Computational neuroscience Cytomegalovirus Cytomegalovirus - immunology Genomics Glioblastoma Glioblastoma - genetics Glioblastoma - virology glioblastoma multiforme Glioma High-Throughput Nucleotide Sequencing high‐throughput sequencing Humans Immunoglobulin G - blood Immunoglobulin M - blood Infectious Causes of Cancer Interferon Interferon Type I - immunology Life Sciences Medical diagnosis Medical research Medical sciences Medical screening metagenomic analysis Metagenomics Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neurology Pathogenesis RNA viruses Simian virus 40 Targeted cancer therapy Therapeutic targets Tumors Tumors of the nervous system. Phacomatoses virus discovery Viruses Nervous system diseases Nucleotide sequence Cytokine Malignant tumor Glioblastoma multiforme Virus Malignant glioma metagenomic analysis Cancerology Gene Central nervous system disease virus discovery Antiviral Genetics Interferon antiviral type I interferon response Sequencing high-throughput sequencing Cancer glioblastoma multiforme
ISSN:	0020-7136, 1097-0215, 1097-0215
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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. What's new? Glioblastoma remains frustratingly difficult to cure. There is some evidence to suggest viruses might contribute to glioblastoma, a very tempting possibility, as the involvement of a virus could open doors to formulating novel treatments. However, the role of viruses is still vague and controversial. In this study the authors have developed a robust megagenomic approach to search tumor tissue for the presence of viruses, the first of its kind. They found no common or recurring active viruses, although they did detect a non‐specific interferon pattern resembling an antiviral response.
AbstractList	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.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. 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. What's new? Glioblastoma remains frustratingly difficult to cure. There is some evidence to suggest viruses might contribute to glioblastoma, a very tempting possibility, as the involvement of a virus could open doors to formulating novel treatments. However, the role of viruses is still vague and controversial. In this study the authors have developed a robust megagenomic approach to search tumor tissue for the presence of viruses, the first of its kind. They found no common or recurring active viruses, although they did detect a non‐specific interferon pattern resembling an antiviral response. 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. What's new? Glioblastoma remains frustratingly difficult to cure. There is some evidence to suggest viruses might contribute to glioblastoma, a very tempting possibility, as the involvement of a virus could open doors to formulating novel treatments. However, the role of viruses is still vague and controversial. In this study the authors have developed a robust megagenomic approach to search tumor tissue for the presence of viruses, the first of its kind. They found no common or recurring active viruses, although they did detect a non-specific interferon pattern resembling an antiviral response. [PUBLICATION 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. 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. What's new? Glioblastoma remains frustratingly difficult to cure. There is some evidence to suggest viruses might contribute to glioblastoma, a very tempting possibility, as the involvement of a virus could open doors to formulating novel treatments. However, the role of viruses is still vague and controversial. In this study the authors have developed a robust megagenomic approach to search tumor tissue for the presence of viruses, the first of its kind. They found no common or recurring active viruses, although they did detect a non-specific interferon pattern resembling an antiviral response. 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. What's new? Glioblastoma remains frustratingly difficult to cure. There is some evidence to suggest viruses might contribute to glioblastoma, a very tempting possibility, as the involvement of a virus could open doors to formulating novel treatments. However, the role of viruses is still vague and controversial. In this study the authors have developed a robust megagenomic approach to search tumor tissue for the presence of viruses, the first of its kind. They found no common or recurring active viruses, although they did detect a non‐specific interferon pattern resembling an antiviral response.
Author	Zdobnov, Evgeny M. Cosset, Érika Kaiser, Laurent Petty, Tom J. Amar El‐Dusouqui, Soraya Cordey, Samuel Farinelli, Laurent Tirefort, Diderik Dietrich, Pierre‐Yves Rigal, Emmanuel Padioleau, Ismael Preynat‐Seauve, Olivier Nayernia, Zeynab Dutoit, Valérie Krause, Karl‐Heinz Otten‐Hernandez, Patricia Bruyère‐Cerdan, Pascale
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Copyright_xml	– notice: 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC – notice: 2015 INIST-CNRS – notice: 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC. – notice: 2013. This article is published under http://creativecommons.org/licenses/by-nc-nd/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: Distributed under a Creative Commons Attribution 4.0 International License – notice: 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC 2013
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Keywords	Nervous system diseases Nucleotide sequence Cytokine Malignant tumor Glioblastoma multiforme Virus Malignant glioma metagenomic analysis Cancerology Gene Central nervous system disease virus discovery Antiviral Genetics Interferon antiviral type I interferon response Sequencing high-throughput sequencing Cancer glioblastoma multiforme
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Notes	E.C. and T.J.P. contributed equally to this study. The authors declare no conflict of interest. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Grant sponsor: The 3R Research Foundation (to O.P.-S.), The ARTERES Foundation (to O.P.-S. and K.-H.K.), The ISREC Foundation (to O.P.-S.), The Egon Naef Foundation (to O.P.-S.), The Louis Jeantet Foundation (to L.K. and E.M.Z.)
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Snippet	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...
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SubjectTerms	Antibodies, Viral - blood Antiviral drugs antiviral type I interferon response Biological and medical sciences Biopsy Brain cancer Brain Neoplasms - genetics Brain Neoplasms - immunology Brain Neoplasms - virology Brain tumors Cancer Computational neuroscience Cytomegalovirus Cytomegalovirus - immunology Genomics Glioblastoma Glioblastoma - genetics Glioblastoma - virology glioblastoma multiforme Glioma High-Throughput Nucleotide Sequencing high‐throughput sequencing Humans Immunoglobulin G - blood Immunoglobulin M - blood Infectious Causes of Cancer Interferon Interferon Type I - immunology Life Sciences Medical diagnosis Medical research Medical sciences Medical screening metagenomic analysis Metagenomics Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neurology Pathogenesis RNA viruses Simian virus 40 Targeted cancer therapy Therapeutic targets Tumors Tumors of the nervous system. Phacomatoses virus discovery Viruses
Title	Comprehensive metagenomic analysis of glioblastoma reveals absence of known virus despite antiviral‐like type I interferon gene response
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