Exome sequencing of EBV driven lymphoma
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ABSTRACT:
PROVIDER: EGAS00001001021 | EGA |
REPOSITORIES: EGA
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Project description:Exome sequencing of a case of lethal EBV-driven LPD
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Project description:Our group has previously identified how PARP1 can control EBV latency by: (1) altering the 3D virus chromatin structure [28]; (2) regulating CTCF binding on EBV promoters and supporting the latency expression program [29-32]; (3) repressing the lytic gene expression by binding BZLF1 promoter [33, 34]. To date, the therapeutic effect of PARP1 inhibitors on EBV+ lymphomagenesis has been poorly explored. Therefore, we aimed to investigate whether PARP1i was able to counteract EBV-driven tumors in a LCL xenograft model and identify, and confirm, possible mechanisms underlying its therapeutic effect. In the present study we demonstrate that PARP1 inhibition restricts EBV-driven lymphoma in vivo, pointing out the oncogene MYC as its functional target. Specifically, PARP1 inhibition reverts the tumor growth and the metastatic potential of EBV+ LCL, inducing a dramatic transcriptional reprogramming. Interestingly, the absence of PARP1 activity causes a decrease in MYC expression, subsequently leading to a dysregulation of MYC-associated co-factors and targets, both in vivo and in vitro. Our findings also corroborate the link between PARP1 and EBNA2 expression, that we previously demonstrated in vitro. Overall, our study strengthens the central role of PARP1 in EBV malignant transformation and outlines the EBNA2/MYC pathway as an additional target of PARP1 regulation in LCL
2024-06-27 | GSE236050 | GEO
Project description:Epstein Barr Virus (EBV) driven B-cell neoplasms arise from reactivation of latently infected B-cells. In a subset of patients EBV drives a polymorphous lymphoproliferative disorder (LPD) in which B-cell differentiation is retained. Spontaneous EBV reactivation following B-cell mitogen stimulation provides a potential model of polymorphic EBV-driven LPD. We have developed an in vitro model of plasma cell (PC) differentiation from peripheral blood memory B-cells. To assess the frequency and phenotypes of EBV-associated populations derived during differentiation we analyzed 8 differentiations at the PC stage, with a targeted single cell gene expression panel. We identified subpopulations of EBV-gene expressing cells with PC and/or B-cell expression features in differentiations from all tested donors. EBV-associated cells varied in frequency ranging from 3-28% of cells. Most EBV-associated cells expressed PC genes such as XBP1 or MZB1 and in all samples these included a quiescent PC fraction lacking cell cycle gene expression. With increasing EBV-associated cells, populations with B-cell features became prominent, co-expressing germinal centre (GC) and activated B-cell gene patterns. The presence of highly proliferative EBV-associated cells was linked to retained MS4A1/CD20 expression and IGHM and IGHD co-expression, while IGHM only and class-switched cells were enriched in quiescent PC fractions. Thus, patterns of gene expression in primary EBV reactivation are consistent with recently proposed models relating EBV-mediated transformation in lymphoblastoid cell lines to features of GC B-cells, and suggest a particular association between spontaneously developing EBV-expansions and IgM+ IgD+ non-switched B-cells.
2023-06-14 | GSE232418 | GEO
Project description:We examined the viral epitranscriptome in EBV transformed lymphoblastoid cell lines (LcLs) and EBV-positive Burkitt's lymphoma, Akata cells, using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Biological replicates of ribo-RNA deleted mRNA of each cell type were prepared for MeRIP-seq followed by peak calling using the exome Peak package with settings for stringent peak calling on both strands of the genome.
2023-08-12 | GSE129217 | GEO
Project description:Extranodal NK/T-cell, nasal type (hereinafter, nasal T/NK lymphoma), is a distinct clinicopahtologic entity highly associated with EBV. Among nasal T/NK lymphoma, some cases are developed from the long-lasting EBV infection termed chronic active EBV (CAEBV) infection.The clonal expansion of EB infected T- or NK cell are seen in patients with both nasal T/NK lymphoma and CAEBV infection, suggesting that two diseases might partly share the similar mechanism by which EBV affect host cellular genes. Question has thus arisen why a subset of patients with CAEB infection develop into nasal T/NK lymphoma. This study aimed to investigate the virus-host interaction in EBV-associated lymphoma. Keywords = nasak NK/T lymphoma Keywords = chronic active EBV infection Keywords: other
2006-01-11 | GSE2432 | GEO
Project description:Background: In several types of malignancies, especially EBV-associated nasopharyngeal carcinomas, high Galectin-9 (Gal-9) expression is indicative of an aggressive tumor phenotype. The contribution of Gal-9 to the oncogenesis of B-cell lymphomas (BCLs) has not yet been investigated. Methods: The expression of Gal-9, STING, and EBNA1 was measured by immunohistochemical (IHC) staining on tumor sections from 66 BCL patients. Artificial EBV infection of normal primary B cells in vitro was used as an experimental model. The dynamic changes of the transcriptome of EBV-infected B cells undergoing transformation were investigated by bulk RNA-sequencing and bioinformatics analysis. The oncogenic role of Gal-9 was investigated in vitro by addition of recombinant Gal-9 to EBV-infected primary B-cells, and growth assays. The underlying molecular mechanisms were investigated by immunoblotting and immunofluorescent (IF) staining, CHIP and luciferase reporter assays. Results: In clinical specimens of BCLs, Gal-9 expression was significantly associated with tumor stage, latent EBV infection and abundance of the viral latent protein EBNA1. Looking at the transcriptome changes occurring in vitro during EBV-driven B-cell transformation, we could identify a series of genes undergoing long term activation and remaining highly expressed in mature LCLs. The Gal-9 gene is one of them. Its expression is enhanced during the transformation process at the mRNA level and even more at the protein level. This up-regulation results at least in part from its transactivation by EBNA1 which can bind its promoter. Reciprocally, we find that addition of extra-cellular Gal-9 promotes B-cell transformation and establishment of the latent phase of EBV-infection. Concomitantly, extra-cellular Gal-9 blocks STING signaling and enhances STAT3 phosphorylation. Inhibition of Sting signaling or STAT3 phosphorylation blocks B-cell transformation, even in the presence of Gal-9. Conclusion: our data unveil a role of amplification and acceleration for Gal-9 in the process of EBV-driven B-cell transformation. This process might be relevant to the pathogenesis of EBV-associated BCLs.
2022-06-30 | GSE162516 | GEO
Project description:Nasal T/NK lymphoma is a unique subtype of non-Hodgkin lymphoma (NHL) that is aggressive and incurable closely associated with Epstein-Barr virus (EBV)3. The clonal expansion of EB infected T- or NK cell is also seen in patients with chronic active EBV (CAEBV) infection, suggesting that two diseases might partly share a similar mechanism by which EBV affect host cellular genes. In order to understand the pathogenesis of EBV-associated T/NK lymphoproliferative disorders (LPD) and design new therapies, we employed a novel EBV DNA microarray to compare patterns of EBV expression in SNK/T cells established from EBV-associated T/NK LPD. Keywords: parallel sample
2005-09-20 | GSE2414 | GEO
Project description:Whilst the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognized, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. We have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. Whilst loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. We investigated whether there were common gene expression changes between EBV-positive and loss clones derived for four endemic Burkitt lyphoma cell lines that could explain the apoptosis sensitivity of clones that had lost EBV.
2018-01-25 | GSE100458 | GEO
Project description:A SILAC based experiment of cells infected or uninfected with EBV
2015-11-06 | PXD002461 | Pride
Project description:RNAseq was used to identify host and EBV viral transcriptome changes in CHAF1B knock-out Akata EBV+ cells. CHAF1B KO Akata EBV+ cells were subjected to RNAseq analysis. The Akata EBV+ cells expressing control sgRNA was used as the control.
2020-10-15 | GSE148910 | GEO