The different epidemiologic subtypes of Burkitt Lymphoma share a largely homogenous micro RNA profile distinct from diffuse large B-cell lymphoma.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE22420 | GEO | 2011/07/18
SECONDARY ACCESSION(S): PRJNA128567
REPOSITORIES: GEO
Similar Datasets
Project description:Sporadic Burkitt lymphoma (sBL) can be delineated from diffuse large B-cell lymphoma (DLBCL) by a very homogeneous mRNA expression signature. However, it remained unclear whether all three BL variants – sBL, endemic BL (eBL) and immunodeficiency-associated BL (HIV-BL) – represent a uniform biological entity despite their differences in geographical occurrence, association with immunodeficiency and/or incidence of EBV infection. To address this issue, we generated micro RNA (miRNA) profiles from 18 eBL, 31 sBL and 15 HIV-BL cases. In addition, we analyzed the miRNA expression of 86 DLBCL to determine whether miRNA profiles recapitulate the molecular differences between BL and DLBCL evidenced by mRNA profiling. A signature of 38 miRNAs enriched in MYC regulated and NF-kB pathway associated miRNAs was obtained that differentiated BL from DLBCL. The miRNA profiles of sBL and eBL displayed only 6 differentially expressed miRNAs, whereas HIV and EBV infection had no impact on the miRNA profile of BL. In conclusion, miRNA profiling confirms that BL and DLBCL represent distinct lymphoma categories and demonstrates that the three BL variants are representatives of the same biological entity with only marginal miRNA expression differences between eBL and sBL. Archival tumor specimens of 86 diffuse large B-cell lymphoma (DLBCL) and 64 Burkitt lymphoma (BL) patients were obtained. The DLBCL samples have previously been reviewed by a panel of expert hematopathologists and their clinical data were published as part of the RiCOVER-60 trial. The diagnosis of all BL cases was confirmed by histopathology review according to the criteria of the WHO classification. Based on their geographical origin, 31 BL samples were designated as sporadic BL (sBL) and 18 samples as endemic BL (eBL). Fifteen BL cases were diagnosed as immunodeficiency-associated BL (HIV-BL). Of the 18 eBL 14 cases were EBV+ (87.5%), 2 samples were EBV- (12.5%) and for 2 eBL cases the EBV status was unknown. Of the sBL samples 26 were EBV- (86.7%), 4 cases were EBV+ (13.3%) and for 1 case the EBV status was not evaluable. Among the HIV-BL 5 (33.3%) were EBV+, whereas 10 (66.7%) were EBV-.
2011-07-17 | E-GEOD-22420 | biostudies-arrayexpress
Project description:Burkitt lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL (eBL) in developing countries, necessitating new strategies. The normal germinal center B cell is the presumed cell of origin for both BL and diffuse large B cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may utilize different oncogenic pathways. BL is subdivided into a sporadic subtype (sBL) that is diagnosed in developed countries, the EBV-associated eBL subtype, and an HIV-associated subtype (hivBL), but it is unclear whether these subtypes employ similar or divergent oncogenic mechanisms. Here we used high throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways that cooperate with MYC, the defining oncogene of this cancer. In 70% of sBL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival PI(3) kinase pathway in BL, in part by augmenting tonic B cell receptor signaling. In 38% of sBL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL.
2012-08-16 | GSE35163 | GEO
Project description:EBV-positive cell lines were assayed for expression of EBV miRNAs. The names of the miRNAs are from miRBase from Fall 2007. Microarray probes are tandem complements of the mature miRNA sequence. We assayed Burkitt's lymphoma (BL), Nasopharyngeal carcinoma, post-transplant lymphoproliferative disease (PTLD), primary effusion lymphoma, and lymphoblastoid cell lines. We also assayed primary B cells that were infected with the B95-8 strain of EBV, which was found to express EBV miRNAs as early as 20 hours post infection. We have found PTLD and BLs from HIV-positive donors both express EBV miRNAs. These types of cell lines have not previously been found to express viral miRNAs. We have found that cells that support type I and type II latency express only the BART miRNAs, whereas cells that support type III latency express BART and BHRF1 miRNAs. Furthermore, BL cell lines that spontaneously lose EBV express levels of the viral miRNAs that are at least 5-fold lower than cell lines that do not lose EBV.
2008-12-01 | GSE12014 | GEO
Project description:EBV-positive cell lines were assayed for expression of EBV miRNAs. The names of the miRNAs are from miRBase from Fall 2007. Microarray probes are tandem complements of the mature miRNA sequence. We assayed Burkitt's lymphoma (BL), Nasopharyngeal carcinoma, post-transplant lymphoproliferative disease (PTLD), primary effusion lymphoma, and lymphoblastoid cell lines. We also assayed primary B cells that were infected with the B95-8 strain of EBV, which was found to express EBV miRNAs as early as 20 hours post infection. We have found PTLD and BLs from HIV-positive donors both express EBV miRNAs. These types of cell lines have not previously been found to express viral miRNAs. We have found that cells that support type I and type II latency express only the BART miRNAs, whereas cells that support type III latency express BART and BHRF1 miRNAs. Furthermore, BL cell lines that spontaneously lose EBV express levels of the viral miRNAs that are at least 5-fold lower than cell lines that do not lose EBV. In total, 48 samples have been assayed and included in this study. EBV-negative control samples are not included in this data set, but raw and processed data may be requested from the contributors. These EBV-negative cell lines include the Burkitt's lymphoma cell lines, BJAB and Akata-negative, the gastric carcinoma cell line, AGS, and uninfected primary B cells. Of the 48 samples, we have assayed 22 different EBV-positive cell lines and 4 different time points after infection of primary B cells with EBV. Replicates of the majority of cell lines is included in this data set. Replicates are from independent RNA isolations that were then hybridized to individual microarrays.
2008-11-30 | E-GEOD-12014 | biostudies-arrayexpress
Project description:Burkitt lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL (eBL) in developing countries, necessitating new strategies. The normal germinal center B cell is the presumed cell of origin for both BL and diffuse large B cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may utilize different oncogenic pathways. BL is subdivided into a sporadic subtype (sBL) that is diagnosed in developed countries, the EBV-associated eBL subtype, and an HIV-associated subtype (hivBL), but it is unclear whether these subtypes employ similar or divergent oncogenic mechanisms. Here we used high throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways that cooperate with MYC, the defining oncogene of this cancer. In 70% of sBL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival PI(3) kinase pathway in BL, in part by augmenting tonic B cell receptor signaling. In 38% of sBL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL. Gene expression was analyzed using Agilent human 4X44K oligo gene expression arrays. Cell lines (Namalwa, BL41, Daudi, Defauw, and THOMAS) were infected with control (empty vector, Cy3) paired with ID3 (Cy5) or control (shControl, Cy3) paired with shTCF3 (Cy5) constructs, and changes in gene expression were monitored over time after induction of the constructs with doxycyclin. In Namalwa (n=8) and THOMAS (n=4) cell lines, a four timepoint series (24, 48, 72, 96 hours) of construct induction was analyzed, for a total of 12 arrays. In BL41 (n=4), Daudi (n=4) and Defauw (n=4) cell lines, a two timepoint series (24 and 48 hours) of construct induction was analyzed, for a total of 12 arrays. In addition, two cell lines (Daudi and THOMAS) were treated with Rapamycin (100 pM) and paired with a DMSO control in a four timepoint series (3, 6, 12 and 24 hours) for a total of 8 arrays.
2012-08-16 | E-GEOD-35163 | biostudies-arrayexpress
Project description:Gene expression profiling (GEP) of ARL patient samples was done to determine whether gene expression signatures derived from HIV- lymphomas retained their ability to molecularly classify HIV+ lymphomas. The GEP-based predictors robustly classified ARL tumors, distinguishing molecular Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as well as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) molecular subtypes of DLBCL. Gene expression profiles were used to identify coordinately regulated gene sets and pathways that differ between HIV+ and HIV- lymphomas of corresponding molecular subtype. Frozen tumor biopsies were obtained from 20 HIV-positive patients with an AIDS-defining lymphoma. Cases were ascertained at the University of Nebraska Medical Center and through the NCI AIDS and Cancer Specimen Resource tumor bank. Sufficient RNA for hybridization to Affymetrix U133 plus 2 arrays was obtained on 17 ARL cases. Details of all 20 HIV-positive patients can be found in the supplementary file below. Third party array data from HIV- lymphomas of corresponding molecular subtype were used for the comparison and molecular classification of the HIV+ cases in this study. The third party HIV- lymphoma samples include the following. [1] HIV- lymphoma, BL cases: 84 samples profiled on the Affymetrix HG U133 Plus 2 array. The data are publicly available on the website companion to Dave et al. NEJM 2006; Volume 354:13-24 (http://llmpp.nih.gov/BL/) and were used 'as is' (ie, not reanalyzed). [2] HIV- lymphoma, DLBCL cases: 200 of the 414 cases in Series GSE10846 (listed in the supplementary file below). These included all R-CHOP treated cases of either ABC or GCB subtype. These data were also used as is. These data were published in Lenz et al. NEJM 2008; Volume 359: 2313-2323.
2012-07-17 | E-GEOD-17372 | biostudies-arrayexpress
Project description:Gene expression profiling (GEP) of ARL patient samples was done to determine whether gene expression signatures derived from HIV- lymphomas retained their ability to molecularly classify HIV+ lymphomas. The GEP-based predictors robustly classified ARL tumors, distinguishing molecular Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as well as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) molecular subtypes of DLBCL. Gene expression profiles were used to identify coordinately regulated gene sets and pathways that differ between HIV+ and HIV- lymphomas of corresponding molecular subtype.
2010-03-01 | GSE17189 | GEO
Project description:Gene expression profiling (GEP) of ARL patient samples was done to determine whether gene expression signatures derived from HIV- lymphomas retained their ability to molecularly classify HIV+ lymphomas. The GEP-based predictors robustly classified ARL tumors, distinguishing molecular Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as well as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) molecular subtypes of DLBCL. Gene expression profiles were used to identify coordinately regulated gene sets and pathways that differ between HIV+ and HIV- lymphomas of corresponding molecular subtype.
2012-07-18 | GSE17372 | GEO
Project description:Gene expression profiling (GEP) of ARL patient samples was done to determine whether gene expression signatures derived from HIV- lymphomas retained their ability to molecularly classify HIV+ lymphomas. The GEP-based predictors robustly classified ARL tumors, distinguishing molecular Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as well as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) molecular subtypes of DLBCL. Gene expression profiles were used to identify coordinately regulated gene sets and pathways that differ between HIV+ and HIV- lymphomas of corresponding molecular subtype. Frozen tumor biopsies were obtained from 20 HIV-positive patients with an AIDS-defining lymphoma. Cases were ascertained at the University of Nebraska Medical Center and through the NCI AIDS and Cancer Specimen Resource tumor bank. Sufficient RNA for hybridization to Affymetrix U133 plus 2 arrays was obtained on 17 ARL cases. Details of all 20 HIV-positive patients can be found in the supplementary file linked below.
2010-03-07 | E-GEOD-17189 | biostudies-arrayexpress
Project description:Epstein-Barr virus (EBV) is an oncogenic human herpesvirus involved in the pathogenesis of Burkitt’s lymphoma (BL) and various other lymphoproliferative disorders. In BL, EBV protein expression is restricted to the EBNA-1, but small non-coding RNAs such as the EBERs and micro (mi)RNAs can also be detected. miRNAs play major roles in crucial processes such as proliferation, differentiation and cell death. It has recently become clear that alteration in the expression profile of miRNAs contribute to the pathogenesis of a number of malignancies. During latent infection, EBV expresses 25 viral pre-miRNAs and modulates the expression of specific cellular miRNAs, such as miR-155 and miR-146, which potentially play a role in oncogenesis. Here, we established the small RNA expression profiles of three BL cell lines. Using large-scale sequencing coupled to northern blot and real-time RT-PCR analysis validation, we demonstrated the differential expression of some cellular and viral miRNAs. High-level expression of the miR-183-96-182 cluster and EBV miR-BART cluster was significantly associated with EBV type I latency. This expression was not affected by viral reactivation since TGF-ß1 stimulation did not significantly change the miRNA profiles. However, the expression of latent membrane protein (LMP)-1 triggered down-regulation of the expression of the miR-183-96-182 cluster. We further show that this effect involves the AKT signaling pathway.
2015-09-25 | GSE65752 | GEO