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GSE43677
Homo sapiens
71 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Based on the assumption that molecular mechanisms involved in cancerogenesis are characterized by groups of coordinately expressed genes, we developed and validated a novel method for analyzing transcriptional data called Correlated Gene Set Analysis (CGSA). Using 50 extracted gene sets we identified three different profiles of tumors in a cohort of 364 Diffuse large B-cell (DLBCL) and related mature aggressive B-cell lymphomas other than Burkitt lymphoma. The first profile had high level of expression of genes related to proliferation whereas the second profile exhibited a stromal and immune response phenotype. These two profiles were characterized by a large scale gene activation affecting genes which were recently shown to be epigenetically regulated, and which were enriched in oxidative phosphorylation, energy metabolism and nucleoside biosynthesis. The third and novel profile showed only low global gene activation similar to that found in normal B cells but not cell lines. Our study indicates novel levels of complexity of DLBCL with low or high large scale gene activation related to metabolism and biosynthesis and, within the group of highly activated DLBCLs, differential behavior leading to either a proliferative or a stromal and immune response phenotype.
Publication Title
Massive transcriptional perturbation in subgroups of diffuse large B-cell lymphomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In Burkitt lymphoma (BL), an aggressive germinal-center (GC) derived non-Hodgkin B-cell lymphoma characterized by MYC translocations as early transforming event, the apoptotic properties of MYC must have been overcome by pro-survival signals. Whereas activation of the pro-survival factor NFkappaB is not eminent in BL, PI3K signalling, which mediates B cell receptor associated survival signals in mature B cells, might be the cooperating event. Here we prove this hypothesis by the generation of BL in mice upon concordant expression of MYC and activation of PI3K in GC B cells. Unlike existing murine BL-like models, our tumour model fully phenocopies primary human BL and reflects the complexity of the disease with regard to histological appearance, surface marker expression, and characteristic gene expression profiles. Like in human BL, tumour monoclonality indicated a multistep pathogenesis underlining MYC and PI3K as predisposing events that invariably lead to GC-derived BL formation. In accordance, copy number alteration analysis revealed genomic regions involved in BL pathogenesis.
Publication Title
Synergy between PI3K signaling and MYC in Burkitt lymphomagenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 148 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Characterization of genomic imbalances in diffuse large B-cell lymphoma by detailed SNP-chip analysis.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 148 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
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.
Publication Title
Characterization of genomic imbalances in diffuse large B-cell lymphoma by detailed SNP-chip analysis.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
MYC translocations are the biologic hallmark of Burkitt lymphomas but also occur in other mature B-cell lymphomas. If accompanied by chromosomal breaks targeting the BCL2 and/or BCL6 oncogenes, these MYC translocation-positive (MYC+) lymphomas are called double-hit lymphomas (DHLs); otherwise, the term single-hit lymphoma (SHL) is applied. In order to characterize the biologic features of these MYC+ lymphomas other than Burkitt lymphomas, we explored, after exclusion of molecular Burkitt lymphoma (mBL) as defined by gene expression profiling (GEP), the molecular, pathological and clinical aspects of 80 MYC translocation (MYC+) lymphomas (31 SHL, 26 BCL2+/MYC+, 14 BCL6+/MYC+, 6 BCL2+/BCL6+/MYC+ and 3 MYC+ lymphomas with unknown BCL6 status). Comparison of SHL and DHL revealed no difference in frequency of MYC partner (IG/non-IG), genomic complexity or MYC expression and no differences in GEP. DHL showed a more frequent GCB-like GEP and higher IGH and MYC mutation rates. GEP revealed 130 differentially expressed genes between BCL6+/MYC+ and BCL2+/MYC+ DHL. BCL2+/MYC+ DHL showed a more frequent GCB-like GEP. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In contrast to mBL and lymphomas without MYC break, SHL and DHL patients had similar poor outcome. Our data suggest that after excluding mBL, MYC+ lymphomas could be biologically widely lumped without further need for subclassification.
Publication Title
Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The spectrum of entities, the therapeutic strategy and the outcome of mature aggressive B-cell lymphomas (maB-NHL) differs between children and adolescents on the one hand and adult patients on the other. Whereas adult maB-NHL have been studied in detail, data on molecular profiling of pediatric maB-NHL are hitherto lacking. Our aim was to characterize pediatric maB-NHL on the molecular level and to evaluate whether a molecular diagnosis of pediatric maB-NHL reveals clinically relevant groups.
Publication Title
Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 219 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The distinction between the Burkitt lymphoma and diffuse large B-cell lymphoma is imprecise using current diagnostic criteria. We applied transcriptional and genomic profiling to molecularly define Burkitt lymphoma. Gene expression profiling employing Affymetrix GeneChips (U133A) was performed in 220 mature aggressive B-cell lymphomas, including a core group of eight Burkitt lymphomas, which fulfilled all diagnostic criteria of the WHO classification. A molecular signature of Burkitt lymphoma was generated. Chromosomal abnormalities were detected by interphase fluorescence in-situ hybridization and array comparative genomic hybridization. The molecular Burkitt lymphoma signature identified 44 cases. Fifteen of these cases lacked a morphology typical for Burkitt/Burkitt-like lymphoma. The vast majority (88%) of the 176 lymphomas without the molecular Burkitt lymphoma signature represented diffuse large B-cell lymphomas. In 20% of these cases a MYC break was detectable which was associated with complex chromosomal changes. Our molecular definition of Burkitt lymphoma sharpens and extends the spectrum of Burkitt lymphoma. In mature aggressive B-cell lymphomas without a Burkitt lymphoma signature, a chromosomal break in the MYC locus proved to be associated with adverse clinical outcome.
Publication Title
A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Burkitt lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma (B-NHL), which originates from germinal center (GC) B cells and harbors translocations deregulating the MYC oncogene. A comparative analysis of microRNAs (miRNAs) expressed in normal and malignant GC B cells identified miR-28 as significantly down-regulated in BL, as well as in other GC-derived B-NHL. We show that re-expression of miR-28 impairs cell growth and clonogenic properties of BL cells by modulating several targets including MAD2L1, a component of the spindle checkpoint whose down-regulation is essential in mediating miR-28-induced growth-arrest, and BAG1, an activator of the ERK pathway.
Publication Title
MicroRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 271 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background: Germinal center B-cell (GCB) lymphomas are common in children and adults. The prognosis strongly depends on age. Subgroups of GCB-lymphomas are characterized by chromosomal translocations affecting immunoglobulin (IG) loci leading to oncogene deregulation.
Publication Title
Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Toxoplasma strains are known to inhibit the expression of several interferon-gamma induced genes, and a type II strain was shown to dysregulate genome-wide responses to interferon-gamma in human fibroblasts (Kim et al., 2007, J Immunol.). In this study we aimed to determine the effect of infection with three clonal lineages of Toxoplasma, type I, II, and III strains on genome-wide interferon-gamma induced transcription in murine macrophages. We also assessed the effect of the two main Toxoplasma modulators of mouse macrophage transcription, ROP16 and GRA15 (Jensen et al., 2011, Cell Host Microbe).
Publication Title
Toxoplasma gondii clonal strains all inhibit STAT1 transcriptional activity but polymorphic effectors differentially modulate IFNγ induced gene expression and STAT1 phosphorylation.
Sample Metadata Fields
Specimen part
View Samples