Presence of Viral DNA in Whole-Genome Sequencing of Brain Tumor Tissues from The Cancer Genome Atlas

Amirian, E. Susan; Bondy, Melissa L.; Mo, Qianxing; Bainbridge, Matthew N.; Scheurer, Michael E.

doi:10.1128/jvi.02725-13

Cited by 12 publications

(11 citation statements)

References 5 publications

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“…Nevertheless, this approach also failed to identify any meaningful virus associations in the analyzed samples. This is in contrast to a report by Amirian et al in which they identified HHV-6A and HHV-6B in the WGS datasets from TCGA [ 5 ]. Another study conducted by Cimino et al also identified HHV-6 and EBV DNA when they analyzed unmapped reads from a NGS-based comprehensive oncology panel [ 9 ].…”

Section: Discussioncontrasting

confidence: 99%

A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus - tumor association

Strong¹,

Blanchard

Lin³

et al. 2016

acta neuropathol commun

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Next generation sequencing (NGS) can globally interrogate the genetic composition of biological samples in an unbiased yet sensitive manner. The objective of this study was to utilize the capabilities of NGS to investigate the reported association between glioblastoma multiforme (GBM) and human cytomegalovirus (HCMV). A large-scale comprehensive virome assessment was performed on publicly available sequencing datasets from the Cancer Genome Atlas (TCGA), including RNA-seq datasets from primary GBM (n = 157), recurrent GBM (n = 13), low-grade gliomas (n = 514), recurrent low-grade gliomas (n = 17), and normal brain (n = 5), and whole genome sequencing (WGS) datasets from primary GBM (n = 51), recurrent GBM (n = 10), and normal matched blood samples (n = 20). In addition, RNA-seq datasets from MRI-guided biopsies (n = 92) and glioma stem-like cell cultures (n = 9) were analyzed. Sixty-four DNA-seq datasets from 11 meningiomas and their corresponding blood control samples were also analyzed. Finally, three primary GBM tissue samples were obtained, sequenced using RNA-seq, and analyzed. After in-depth analysis, the most robust virus findings were the detection of papillomavirus (HPV) and hepatitis B reads in the occasional LGG sample (4 samples and 1 sample, respectively). In addition, low numbers of virus reads were detected in several datasets but detailed investigation of these reads suggest that these findings likely represent artifacts or non-pathological infections. For example, all of the sporadic low level HCMV reads were found to map to the immediate early promoter intimating that they likely originated from laboratory expression vector contamination. Despite the detection of low numbers of Epstein-Barr virus reads in some samples, these likely originated from infiltrating B-cells. Finally, human herpesvirus 6 and 7 aligned viral reads were identified in all DNA-seq and a few RNA-seq datasets but detailed analysis demonstrated that these were likely derived from the homologous human telomeric-like repeats. Other low abundance viral reads were detected in some samples but for most viruses, the reads likely represent artifacts or incidental infections. This analysis argues against associations between most known viruses and GBM or mengiomas. Nevertheless, there may be a low percentage association between HPV and/or hepatitis B and LGGs.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0338-z) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 99%

A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus - tumor association

Strong¹,

Blanchard

Lin³

et al. 2016

acta neuropathol commun

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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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“…The advantage of this technology is that a higher coverage of the target region and thus detection of rare variants is achieved. By means of PCR, BEAMing, and targeted NGS, known (point) mutations can be detected while whole genome or whole exome sequencing may identify unknown mutations, chromosomal aberrations, and altered numbers of copies as well as viral DNA sequences and their integration sites in the human genome 240 . Disadvantages of NGS technology for application in this routine are still the high costs, the precondition of high-quality DNA as well as the abundance of generated data that have to be analyzed and interpreted.…”

Section: Follow-upmentioning

confidence: 99%

HPV – Das andere Kopf-Hals-Karzinom

et al. 2018

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Head and neck cancer is the sixth most common cancer with over 500000 annually reported incident cases worldwide. Besides major risk factors tobacco and alcohol, oropharyngeal squamous cell carcinomas (OSCC) show increased association with human papillomavirus (HPV). HPV-associated and HPV-negative OSCC are 2 different entities regarding biological characteristics, therapeutic response, and patient prognosis. In HPV OSCC, viral oncoprotein activity, as well as genetic (mutations and chromosomal aberrations) and epigenetic alterations plays a key role during carcinogenesis. Based on improved treatment response, the introduction of therapy de-intensification and targeted therapy is discussed for patients with HPV OSCC. A promising targeted therapy concept is immunotherapy. The use of checkpoint inhibitors (e.g. anti-PD1) is currently investigated. By means of liquid biopsies, biomarkers such as viral DNA or tumor mutations in the will soon be available for disease monitoring, as well as detection of treatment failure. By now, primary prophylaxis of HPV OSCC can be achieved by vaccination of girls and boys.

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Presence of Viral DNA in Whole-Genome Sequencing of Brain Tumor Tissues from The Cancer Genome Atlas

Cited by 12 publications

References 5 publications

A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus - tumor association

A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus - tumor association

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

HPV – Das andere Kopf-Hals-Karzinom

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