Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA94675 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, with at least one-third of its patients not responding to the current chemotherapy regimen, R-CHOP. By gene expression profiling, patients with DLBCL can be categorized into two clinically relevant subtypes: activated B-cell (ABC) DLBCL and germinal center B-cell (GCB). Patients with ABC DLBCL have a worse prognosis, and are defined by chronic, overactive signaling through the B-cell receptor and NF-κB pathways. We examined the effects of the Src family kinase (SFK) inhibitor dasatinib in a panel of ABC and GCB DLBCL cell lines, and found that the ABC DLBCL cell lines are much more sensitive to dasatinib than the GCB DLBCL cell lines. However, using multiplexed inhibitor bead coupled to mass spectrometry (MIB/MS) kinome profiling competition and western blot analysis, both subtypes display inhibition of the SFKs in response to dasatinib after both short- and long-term treatment. MIB/MS analyses revealed several cell cycle kinases, including CDK4, CDK6, and the Aurora kinases, are inhibited by dasatinib treatment in the ABC DLBCL subtype, but not in the GCB DLBCL subtype. The present findings have important implications for the clinical use of dasatinib for the treatment of ABC DLBCL, either alone or in combination with other agents.
2018-12-14 | PXD009380 | Pride
Project description:The goal of this study is to identify the transcriptome differences between the two major subtypes of diffuse large B cell lymphoma (DLBCL). DLBCL is the most common form of non-Hodgkin’s lymphoma and has two major subtypes: germinal center B-cell-like (GCB) and activated B-cell-like (ABC). When compared to the GCB form, ABC lymphomas respond much more poorly to current therapies. To investigate how gene expression changes might contribute to this aggressive phenotype, we have used RNA-Seq to profile the whole transcriptome in 8 DLBCL cell lines (4 GCB subtype, 4 ABC) that are derived from patient tumors. 1,545 genes are differentially expressed between subtypes (FDR < 0.05), approximately 7% of the transcriptome. The vast majority of these genes (81%, n = 1251) are more highly expressed in the ABC cell lines. In contrast, only 294 genes (19%) are more highly expressed in the GCB cell lines. Half (n = 765) of the genes with greater ABC subtype expression demonstrate very low read counts (< 5) in the GCB cell types. Conversely, only 21 genes that are more highly expressed in GCB are unique to that subtype. The prevalence of such “on/off” genes indicates that the major differences between ABC and GCB DLBCL are due almost exclusively to additional gene expression in ABC, rather than the two subtypes having divergent but equally active genetic programs. Measurement and comparison of gene expression in 8 cell lines representing the 2 subtypes of DLBCL. 4 cell lines are subtyped as ABC and 4 are subtyped as GCB. 2 replicates are present for each cell line. (Cell line OCI-Ly19 was not included in the analysis because its gene expression clustered in between the subtypes, probably due to its EBV+ status. However, its sequencing runs have been included for completeness.)
2013-12-16 | E-GEOD-50721 | biostudies-arrayexpress
Project description:The goal of this study is to identify the transcriptome differences between the two major subtypes of diffuse large B cell lymphoma (DLBCL). DLBCL is the most common form of non-Hodgkin’s lymphoma and has two major subtypes: germinal center B-cell-like (GCB) and activated B-cell-like (ABC). When compared to the GCB form, ABC lymphomas respond much more poorly to current therapies. To investigate how gene expression changes might contribute to this aggressive phenotype, we have used RNA-Seq to profile the whole transcriptome in 8 DLBCL cell lines (4 GCB subtype, 4 ABC) that are derived from patient tumors. 1,545 genes are differentially expressed between subtypes (FDR < 0.05), approximately 7% of the transcriptome. The vast majority of these genes (81%, n = 1251) are more highly expressed in the ABC cell lines. In contrast, only 294 genes (19%) are more highly expressed in the GCB cell lines. Half (n = 765) of the genes with greater ABC subtype expression demonstrate very low read counts (< 5) in the GCB cell types. Conversely, only 21 genes that are more highly expressed in GCB are unique to that subtype. The prevalence of such “on/off” genes indicates that the major differences between ABC and GCB DLBCL are due almost exclusively to additional gene expression in ABC, rather than the two subtypes having divergent but equally active genetic programs.
2013-12-16 | GSE50721 | GEO
Project description:High expression of the FOXP1 transcription factor distinguishes the highly aggressive Activated B Cell (ABC) type of Diffuse Large B Cell Lymphoma (DLBCL) from the more indolent Germinal Center (GCB) DLBCL subtype and is correlated with poor prognosis. A genetic or functional role for FOXP1 in lymphomagenesis and/or tumor maintenance, however, remains unknown. Here, we report that sustained expression of FOXP1 is necessary for ABC DLBCL cell line survival. Genome-wide transcript profiling reveals that FOXP1 acts directly and indirectly by enforcing expression of known ABC DLBCL hallmarks, including the classical NF-kappaB survival pathway. Our data further suggest that FOXP1 maintains the ABC subtype distinction by repressing gene expression programs dominant in GCB DLBCL and supports a model in which the target of ABC DLBCL transformation is a transitory cell type en route from the germinal center B cell to the terminally differentiated plasma cell.
2015-12-01 | GSE64586 | GEO
Project description:Genome wide transcript and target gene profiling reveal that FOXP1 acts directly and indirectly by enforcing known ABC-DLBCL hallmarks, including Chronically Activated B cell receptor Signaling (CABS) and the classical NF-κB survival pathway. Our data further suggest that FOXP1 maintains ABC-subtype distinction by repressing gene expression programs dominant in GCB-DLBCL and support a model in which the normally transitory B cell plasmablast is the target of ABC-DLBCL transformation.
2016-01-03 | GSE63257 | GEO
Project description:Genome wide transcript and target gene profiling reveal that FOXP1 acts directly and indirectly by enforcing known ABC-DLBCL hallmarks, including Chronically Activated B cell receptor Signaling (CABS) and the classical NF-κB survival pathway. Our data further suggest that FOXP1 maintains ABC-subtype distinction by repressing gene expression programs dominant in GCB-DLBCL and support a model in which the normally transitory B cell plasmablast is the target of ABC-DLBCL transformation. ChIP sequenicng was performed for the FOXP1 transcription factor in DLBCL cell lines. Input was sequenced and used as a control.
2016-07-05 | E-GEOD-63257 | biostudies-arrayexpress
Project description:The goal of this study is to identify the effect of the transcription factor STAT3 in the two major subtypes of diffuse large B cell lymphoma (DLBCL). STAT3 is a signal transducer that, when dysregulated, becomes a powerful oncogene found in many human cancers, including DLBCL. DLBCL is the most common form of non-Hodgkin’s lymphoma and has two major subtypes: germinal center B-cell-like (GCB) and activated B-cell-like (ABC). When compared to the GCB form, ABC lymphomas respond much more poorly to current therapies and often exhibit overexpression or overactivation of STAT3. To investigate how STAT3 might contribute to this aggressive phenotype, we have used ChIP-Seq to identify STAT3 binding sites in 8 DLBCL cell lines (4 GCB subtype, 4 ABC) that are derived from patient tumors. 10,337 distinct STAT3 binding regions are occupied in at least two of the eight cell lines. One third (n = 3524) are differentially bound by STAT3 between the two subtypes (FDR < 0.05). More BRs are strongly bound in ABC than in GCB: 44% of differentially bound BRs (n = 1550) show more STAT3 binding in GCB, while 56% (n = 1974) are more strongly bound in ABC. Identification and comparison of STAT3 transcription factor binding sites in 8 cell lines that represent the 2 subtypes of DLBCL. 4 cell lines are subtyped as ABC and 4 are subtyped as GCB. 2-9 replicates and 1 input control are present for each cell line. (Cell line OCI-Ly19 was not included in the final analysis because RNA-Seq showed that its gene expression clustered in between the subtypes, probably due to its EBV+ status. However, its peak calls were used in intermediate steps of the analysis pipeline. Its sequencing runs have been included for completeness.)
2013-12-16 | E-GEOD-50723 | 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 HGU133A arrays were performed according to the manufacturer's directions on RNA extracted from cryopreserved lymph node biopsies of tumor samples.
2014-07-22 | E-GEOD-57611 | 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: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.
2014-07-22 | GSE57611 | GEO