DNA methylation signatures define molecular subtypes of Diffuse Large B Cell Lymphoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE23501 | GEO | 2010/08/09
SECONDARY ACCESSION(S): PRJNA131069
REPOSITORIES: GEO
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Project description:We performed DNA methylation (HELP) and gene expression profiling in 69 samples of diffuse large B cell lymphoma (DLBCL). First, by gene expression, two molecular subtypes of DLBCL termed as germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL were assigned to the 69 DLBCL cases. Then, we performed supervised analysis using HELP data and defined DNA methylation signature differentiating 2 subgroups of DLBCLs. Keywords: DNA methylation profiling
2010-09-03 | GSE23967 | GEO
Project description:We performed DNA methylation (HELP) and gene expression profiling in 69 samples of diffuse large B cell lymphoma (DLBCL). First, by gene expression, two molecular subtypes of DLBCL termed as germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL were assigned to the 69 DLBCL cases. Then, we performed supervised analysis using HELP data and defined DNA methylation signature differentiating 2 subgroups of DLBCLs. Keywords: DNA methylation profiling The retrospective study included DNA extracted from 69 clinical samples. [This Series represents the DNA methylation profiling component of the study.]
2010-09-03 | E-GEOD-23967 | biostudies-arrayexpress
Project description:We performed DNA methylation (HELP array) and gene expression profiling in 69 samples of diffuse large B cell lymphoma (DLBCL). First, by gene expression, two molecular subtypes of DLBCL termed as "germinal center B cell-like" (GCB) and "activated B cell-like" (ABC) DLBCL were assigned to the 69 DLBCL cases. Then, the supervised analysis using HELP data revealed strikingly different DNA promoter methylation patterns in the two molecular DLBCL subtypes. These data provide epigenetic evidence that the DLBCL subtypes are distinct diseases that utilize different oncogenic pathways. The retrospective study included RNA and DNA extracted from 69 clinical samples. This submission represents the gene expression component of the study.
2010-08-08 | E-GEOD-23501 | biostudies-arrayexpress
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: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 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.
2013-12-16 | GSE50723 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL) is currently divided into three main molecular subtypes, defined by gene expression profiling (GEP): Germinal Center B-cell like (GCB), Activated B-Cell like (ABC), and Primary Mediastinal B-cell Lymphoma (PMBL). DLBCL subtypes were determined according to patients' gene expression profiles.
2017-01-30 | GSE87371 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, including two main molecular subtypes termed activated B cell-like (ABC) and germinal center B cell-like (GCB). ABC DLBCL is less curable and identification of new molecular targets is needed for the development of effective therapeutic agents. Here, we focused on EGR1, a transcription factor that is regulated by the B cell receptor and JAK1/STAT3 signaling pathway in ABC DLBCL. ChIP-Seq and RNA-Seq analyses revealed that gene regulation by EGR1 in ABC DLBCL accentuates multiple oncogenic pathways, including MYC and E2F, while dampening the lethal type I IFN pathway.
2021-08-06 | GSE123291 | GEO