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

Cosset, Érika; Petty, Tom J.; Dutoit, Valérie; Cordey, Samuel; Padioleau, Ismaël; Otten-Hernandez, P.; Farinelli, Laurent; Kaiser, Laurent; Bruyère‐Cerdan, Pascale; Tirefort, Diderik; El‐Dusouqui, Soraya Amar; Nayernia, Zeynab; Krause, Karl‐Heinz; Zdobnov, Evgeny M.; Dietrich, Pierre‐Yves; Rigal, Emmanuel; Preynat‐Seauve, Olivier

doi:10.1002/ijc.28670

Cited by 45 publications

(48 citation statements)

References 34 publications

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“…There is a surprising similarity to be drawn between foreign viral nucleotide sequences and select ncRNAs silent in normal cells, yet transcribed in cancer cells, activating innate immunity (23,29,(35)(36)(37). We determined that ncRNAs expressed predominantly in normal cells from humans and mice reflect patterns of nucleotide sequence motif avoidance, such as underrepresentation of CpG-containing sequences and reduced UpA, similar to protein-coding RNA.…”

Section: Discussionmentioning

confidence: 98%

Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells

Tanne

Muniz

Puzio-Kuter

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Recent studies have demonstrated abundant transcription of a set of noncoding RNAs (ncRNAs) preferentially within tumors as opposed to normal tissue. Using an approach from statistical physics, we quantify global transcriptome-wide motif use for the first time, to our knowledge, in human and murine ncRNAs, determining that most have motif use consistent with the coding genome. However, an outlier subset of tumor-associated ncRNAs, typically of recent evolutionary origin, has motif use that is often indicative of pathogenassociated RNA. For instance, we show that the tumor-associated human repeat human satellite repeat II (HSATII) is enriched in motifs containing CpG dinucleotides in AU-rich contexts that most of the human genome and human adapted viruses have evolved to avoid. We demonstrate that a key subset of these ncRNAs functions as immunostimulatory "self-agonists" and directly activates cells of the mononuclear phagocytic system to produce proinflammatory cytokines. These ncRNAs arise from endogenous repetitive elements that are normally silenced, yet are often very highly expressed in cancers. We propose that the innate response in tumors may partially originate from direct interaction of immunogenic ncRNAs expressed in cancer cells with innate pattern recognition receptors, and thereby assign a previously unidentified danger-associated function to a set of dark matter repetitive elements. These findings potentially reconcile several observations concerning the role of ncRNA expression in cancers and their relationship to the tumor microenvironment.noncoding RNA | genome evolution | cancer immunology

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Section: Discussionmentioning

confidence: 98%

Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells

Tanne

Muniz

Puzio-Kuter

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Most of this debate stems from the fact that different research groups, often using different assays, have generated evidence to support or refute the presence of HCMV in GBM tumors. There is a large amount of research supporting both sides of this issue (Amirian, Bondy, Mo, Bainbridge, & Scheurer, 2014; Baryawno et al, 2011; Baumgarten et al, 2014; Cosset et al, 2014; Fornara et al, 2016; Hashida et al, 2015; Holdhoff et al, 2015; Joseph, McDermott, Baryshnikova, Cobbs, & Ulasov, 2017; Khoury et al, 2013; Lehrer, Green, Rosenzweig, & Rendo, 2015; Libard et al, 2014; McFaline-Figueroa & Wen, 2017; Prins, Cloughesy, & Liau, 2008; Rahbar et al, 2012; Sardi et al, 2015; Schelhorn et al, 2013; Shamran et al, 2015; Solomon, Ramkissoon, Milner, & Folkerth, 2014; Stangherlin et al, 2016; Strong et al, 2016; Wolmer-Solberg et al, 2013) that we summarize in Fig. 1B–D.…”

Section: Introductionmentioning

confidence: 90%

Lack of human cytomegalovirus expression in single cells from glioblastoma tumors and cell lines

Johnson

Abrams

et al. 2017

J. Neurovirol.

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The relationship between human cytomegalovirus (HCMV) and glioblastoma (GBM) is an ongoing debate with extensive evidence supporting or refuting its existence through molecular assays, pre-clinical studies, and clinical trials. We focus primarily on the crux of the debate, detection of HCMV in GBM samples using molecular assays. We propose that these differences in detection could be affected by cellular heterogeneity. To take this into account we align the single-cell RNA sequencing (scRNA-seq) reads from 5 GBM tumors and 2 cell lines to HCMV, and analyze the alignments for evidence of i) complete viral transcripts and ii) low-abundance viral reads. We found that neither tumor nor cell line samples showed conclusive evidence of full HCMV viral transcripts. We also identified low-abundance reads aligned across all tumors, with two tumors having higher alignment rates than the rest of the tumor samples. This work is meant to rigorously test for HCMV RNA expression at a single cell level in GBM samples and examine the possible utility of single cell data in tumor virology.

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“…Cosset et al, [53] [60] On the other hand, several recent studies have reported no association between HCMV and GBM. One study utilized several approaches including a prospective and retrospective analysis to detect the presence of HCMV in tissue, plasma, and serum of high-grade glioma (HGG) patients.…”

Section: Authors Number Of Samples Analyzed Detection Methods Analytementioning

confidence: 98%

The association between human cytomegalovirus and glioblastomas: a review

Hochhalter¹,

Carr²,

O’Neill³

et al. 2017

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Human cytomegalovirus (HCMV) was reported in glioblastoma multiforme (GBM) over a decade ago and this finding has the potential to increase our understanding of the disease and it offers an alternative tumor-specific therapeutic target. Due of this promise, there is a fair amount of time, energy and money being directed towards understanding and utilizing this connection for eventual therapeutic purposes. Nevertheless, the association between GBM and HCMV remains controversial. Several studies have reported conflicting results, further undermining the potential clinical value of this association. In this review, the authors will discuss the latest developments on this evolving issue. Specifically, the results of the latest studies, both positive and negative, will be discussed. Furthermore, potential theories to explain discrepancies reported in the literature will be proposed. Clinical implications including potential targets for anti-HCMV therapy and the latest developments in anti-HCMV therapy will be presented. Finally, solutions to remedy this controversial issue in neuro-oncology will be offered. ReviewThis is an open access article distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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

Cited by 45 publications

References 34 publications

Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells

Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells

Lack of human cytomegalovirus expression in single cells from glioblastoma tumors and cell lines

The association between human cytomegalovirus and glioblastomas: a review

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