Integrated Copy Number Analysis of Epstein Barr Virus (EBV)-Positive Diffuse Large B-Cell Lymphoma (DLBCL)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Heejei Yoon
PROVIDER: E-MTAB-1971 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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:Molecular pathogenesis of posttransplant (PT) lymphoproliferative disorder, including the most prevalent diffuse large B cell lymphoma (DLBCL), is largely unknown. We have recently showed that Epstein-Barr Virus (EBV)+ and EBV- PT-DLBCL are biologically different, but gene expression profile of the latter lymphoma is similar to that of immunocompetent (IC) DLBCL. To validate these findings on a genomic level, we performed array CGH analysis of 21 EBV+ and 6 EBV- PT-DLBCL, and 11 control IC-DLBCL. Genomic and transcriptomic data were subsequently integrated. Notably, EBV+ and EBV- PT-DLBCL revealed only one shared recurrent imbalance, while EBV- PT-DLBCL displayed at least 10 aberrations recurrent in IC-DLBCL, among others gain of 3/3q and 18q, and loss of 6q23/TNFAIP3 and 9p21/CDKN2A. EBV+ PT-DLBCL showed distinct aberrations, including the most prevalent gain/amplification of 9p24.1 targeting PDCD1LG2/PDL2. Significant differential representation/expression of 3p13/FOXP1 and 9p21/CDKNA2 in EBV+ PT-DLBCL when compared with EBV- PT-/IC-DLBCL, suggests that the oncogene FOXP1 and the tumor suppressor gene CDKNA2 are not implicated in pathogenesis of EBV+ PT-DLBCL. In summary, genomic profiling of PT-/IC-DLBCL confirmed biological distinctness of EBV+ and EBV- PT-DLBCL, and relationship between EBV- PT-DLBCL and IC-DLBCL. These findings support the hypothesis that EBV- PT-DLBCL are coincidental lymphomas in transplant recipients
2015-06-02 | GSE69440 | GEO
Project description:We screened TKI-treated-CML-samples in different-phases based on < or >10% copies of BCR-ABL, undetected and control-samples for generating transcriptomics-profile. Transcriptionally, three clusters were identified which showed correlation with BCR-ABL transcript-levels i.e. <10% copies (I-cluster) , undetectable (II-cluster) and >10% copies (III-cluster). CML-new cases as well as Tyrosiine kinase treated-different phases of CML
2016-02-06 | E-GEOD-77571 | biostudies-arrayexpress
Project description:Epstein Barr virus causes linfectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. These anlyses were undertaken in order to determine what gene expression changes occur as the result of primary Epstein Barr virus infection. Samples were taken both before and following acquisition of the virus for direct comparison of samples for single subjects. These data provide an important first description of the response to natural herepesvirus infection in humans. PBMC were taken before acquisition of EBV, during acute infection, and during latency
2013-12-31 | E-GEOD-45918 | biostudies-arrayexpress
Project description:Proteomic analysis of cytokines in unstimulated oropharyngeal secretions. Epstein-barr virus (EBV) is a type 1 carcinogen which causes many cancers in humans. Here we explored the cytokine involvement of the EBV replication process in the oropharynx. Cytokine interactomic profiles were geneerated to understand the involved signalling pathways in HIV infected group and the healthy group. Proteome profilers were used to understand the major cytokine expression levels that are related to infection and immune regulation. We analyzed unstimulated oropharyngeal samples (UOPS) from 42 healthy subjects and 72 HIV positive subjects using the R & D Proteome Profiler array panels. No techinical replicates were performed. 14 samples in HIV group without therapy (NHAART group); 58 HIV patients with highly active antiretroviral therapy (HAART group); 42 samples in healthy group
2010-04-15 | E-GEOD-21339 | biostudies-arrayexpress
Project description:The pathogenesis of diffuse large B cell lymphomas (DLBCL) is only partly understood. We analyzed 148 DLBCL by high resolution single nucleotide polymorphism (SNP)-chips to characterize genomic imbalances. Seventy-nine cases were of the germinal center B-cell like (GCB) type of DLBCL, 49 of the activated B-cell like (ABC) subtype and 20 were type 3 DLBCL. Twenty-four regions of recurrent genomic gains and 38 regions of recurrent genomic losses were identified over the whole cohort, with a median of 25 imbalances per case for ABC-DLBCL and 19 per case for GCB-DLBCL. Several recurrent copy number changes showed differential frequencies in the GCB- and ABC-DLBCL subgroups, including gains of HDAC7A predominantly in GCB-DLBCL (38% of cases) and losses of BACH2 and CASP8AP2 predominantly in ABC-DLBCL (35%), hinting at disparate pathogenetic mechanisms in these entities. Correlating gene expression and copy number revealed a strong gene dosage effect in all tumors, with 34% of probesets showing a concordant expression change in affected regions. Two new potential tumor suppressor genes emerging from the analysis, CASP3 and IL5RA, were sequenced in 10 and 16 candidate cases, respectively. However, no mutations were found, pointing to a potential haploinsufficiency effect of these genes, considering their reduced expression in cases with deletions. This work thus describes differences and similarities in the landscape of genomic aberrations in the DLBCL subgroups in a large collection of cases, confirming already known targets, but also discovering novel copy number changes with possible pathogenetic relevance. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved lymph node biopsies of tumor samples.
2014-07-22 | E-GEOD-57277 | biostudies-arrayexpress
Project description:A subtype of diffuse large B-cell lymphoma (DLBCL), termed activated B-cell-like (ABC) DLBCL, depends on constitutive NF-kB pathway signaling for survival. Small molecule inhibitors of IkB kinase b (IKKb), a key regulator of the NF-kB pathway, kill ABC DLBCL cells and hold promise for the treatment of this lymphoma type. We conducted an RNA interference genetic screen to investigate potential mechanisms of resistance of ABC DLBCL cells to IKKb inhibitors. We screened a library of small hairpin RNAs (shRNAs) targeting 500 protein kinases for shRNAs that would kill an ABC DLBCL cell line in the presence of a small molecule IKKb inhibitor more effectively than in its absence. Two independent shRNAs targeting IKKa synergized with the IKKb inhibitor to kill three different ABC DLBCL cell lines but were not toxic by themselves. Surprisingly, IKKa shRNAs blocked the classical rather than the alternative NF-kB pathway in ABC DLBCL cells, as judged by inhibition of IkBa phosphorylation. IKKa shRNA toxicity was reversed by coexpression of wild type but not kinase inactive forms of IKKa, suggesting that IKKa may directly phosphorylate IkBa under conditions of IKKb inhibition. These results suggest that therapy for ABC DLBCL may be improved by targeting both IKKa and IKKb. Keywords: compound treatment design Gene expression profiling of OCI-Ly3 cells with or without expressing IKKa shRNA in the presence or absence of 12.5 uM IKKb inhibitor for 2 and 3 days. Four samples were analyzed.
2009-06-01 | E-GEOD-11902 | biostudies-arrayexpress
Project description:A major challenge to the study of tumor DNA copy number (CN) in clinical specimens is the lack of appropriate fresh frozen samples and thus a dependence on Formalin-Fixed Paraffin Embedded (FFPE) banked samples, which typically have more extensive clinical follow up information. However, on most high density CN platforms, DNA from FFPE tissues generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from DNA isolated from cell lines and frozen tumor samples. Since the MIP probes require only a small (~40 bp) target binding site, we reasoned they may be well suited to assess FFPE samples. In this study, we successfully applied MIP technology with a panel of 50,000 markers to CN determination in FFPE samples. Using an input of 37 ng genomic DNA, we demonstrated high quality CN data with MIP technology from 93 FFPE samples from seven diverse collections. We found that the performance of FFPE DNA for CN determination was comparable to that of DNA obtained from matched frozen tumor, with only a modest loss in performance of DNA. Tumor FFPE were analyzed using matched normal FFPE as the reference. Tumor and normal pairs: 01-02, 12-13, 16-17, 08-09, 20-21, 24-25, 28-29, and 35-36. Tumor 32 has no matched normal sample.
2009-01-22 | E-GEOD-14353 | biostudies-arrayexpress
Project description:Familial cases of MPN are usually transmitted by autosomal inheritance with incomplete penetrance, appear in adulthood, and demonstrate acquired genetic abnormalities that are similar to those identified in sporadic cases such as JAK2V617F and TET2 mutations. Linkage and segregation analyses indicate that genetic predisposition to MPN cannot be related to a common alteration and rather involves a number of susceptibility loci responsible for independent familial aggregations. Identification of these susceptibility loci may improve our understanding of the mechanisms of predisposition, which may result either in the induction of a genetic instability, favoring the acquisition of oncogenic mutations or corresponds to a fertile ground for selection of somatic mutations. Here, we describe a newly identified germline copy number variation (CNV) that predisposes to essential thrombocythemia (ET) which rapidly progress to myelofibrosis (MF) and MDS/AML. Using induced pluripotent stem and primary cells to explore hematopoietic differentiation, we demonstrate that overexpressed ATG2B and GSKIP enhance hematopoietic progenitor differentiation, including megakaryocytic through increasing their sensitivity to TPO. To evaluate the overexpression of ATG2B and GSKIP in patients and their role in hematopoiesis, we generated EBV cell lines from peripheral blood of patients or relatives. These cell lines were cultured in RPMI with 20% FBS. The present study concerns gene expression of EBV cell lines from patients and controls after RNA extraction (qiagen kit). Gene expression was performed in single color on Agilent8x60K v2 Human whole genome (design 039494) in replicates 15 cell lines from affected patients and 9 non affected controls).
2015-08-17 | E-MTAB-3570 | biostudies-arrayexpress
Project description:Primary Effusion Lymphoma (PEL) is a Diffuse-Large B-cell Lymphoma (DLBCL) with poor prognosis. 100% of PEL carry the genome of Kaposi's Sarcoma-associated herpesvirus (KSHV) and approximately half are co-infected with Epstein-Barr virus (EBV). We profiled genomic aberrations in PEL using the Affymetrix 6.0 SNP array. This identified for the first time individual genes that are altered in PEL. 10/13 (76%) samples were deleted for both the fragile site tumor suppressors WWOX and FHIT. Alterations were also observed in: DERL1, ETV1, RASA4, TPK1, TRIM56 and VPS41 genes, which are yet to be characterized for their roles in cancer. Co-infection with EBV was associated with significantly fewer gross genomic aberrations. PEL could be segregated into EBV positive and EBV negative clusters on the basis of host chromosome alterations. The genomic signature of PEL cells in culture was analogous to those explanted from xenograft tumors. This suggests a model in which both host and virus contribute to the PEL phenotype. 17 samples (no replicates) were analyzed using Partek Genomic Suite software
2011-06-23 | E-GEOD-25839 | biostudies-arrayexpress