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DNA Methyltransferase 1 and DNA Methylation Patterning Contribute to Germinal Center B-Cell Differentiation

ABSTRACT: We performed DNA methylation (HELP) and gene expression profiling in 17 samples of purified Germinal center B cells (GCBs) and Naive B cells (NBC). We performed supervised analysis using HELP data and defined DNA methylation signature differentiting 2 subgroups of B cvells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31671 | GEO | 2011/09/01

SECONDARY ACCESSION(S): PRJNA145385

REPOSITORIES: GEO

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DNA Methyltransferase 1 and DNA Methylation Patterning Contribute to Germinal Center B-Cell Differentiation

Project description:We performed DNA methylation (HELP) and gene expression profiling in 17 samples of purified Germinal center B cells (GCBs) and Naive B cells (NBC). We performed supervised analysis using HELP data and defined DNA methylation signature differentiting 2 subgroups of B cvells. Study included purification of human B cells form reactive tonsils, DNA purification and DNA methylation analysis using HELP assay.

2011-08-31 | E-GEOD-31671 | biostudies-arrayexpress

DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation.

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Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis.

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DNA methylation profiling in primary Diffuse Large B cell Lymphoma (DLBCL) and normal Germinal Center B Cells

Project description:Diffuse Large B-Cell Lymphoma (DLBCL) is the most common aggressive form of non-Hodgkin lymphoma with variable biology and clinical behavior. The current classification does not fully explain the biological and clinical heterogeneity of DLBCLs. In this study we carried out genome-wide DNA methylation profiling of 140 DLBCL samples and 10 normal germinal center B-cells (NGCBs) using the HELP assay and hybridization to a custom Roche NimbleGen promoter array. We defined methylation disruption as a main epigenetic event in DLBCLs and designed a method for measuring the methylation variability of individual cases. We then used a novel approach for unsupervised hierarchical clustering based on the extent of DNA methylation variability. This approach identified 6 clusters (A-F). The extent of methylation variability was associated with survival outcomes, with significant differences in overall and progression-free survival. The novel clusters are characterized by disruption of specific biological pathways like cytokine-mediated signaling, ephrin signaling and pathways associated with apoptosis and cell cycle regulation. In a subset of patients, we profiled gene expression and genomic variation to investigate their interplay with methylation changes. This study is the first to identify novel epigenetic clusters of DLBCLs and their aberrantly methylated genes, molecular associations and survival. DNA methylation profiling in 140 primary denovo Diffuse Large B cell Lymphoma (DLBCL) samples from patients that had undergone R-CHOP chemotherapy and 10 purified normal Germinal Center B Cells

2014-01-18 | E-GEOD-54200 | biostudies-arrayexpress

DNA methylation signatures define molecular subtypes of Diffuse Large B Cell Lymphoma

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

DNA methylation signatures define molecular subtypes of Diffuse Large B Cell Lymphoma

2010-09-03 | GSE23967 | GEO

DNA methylation profiling in primary Diffuse Large B cell Lymphoma (DLBCL) and normal Germinal Center B Cells

2014-01-18 | GSE54200 | GEO

DNA Methylation Dynamics of Germinal Center B Cells Are Mediated by AID

Project description:Changes in DNA methylation are required for the formation of germinal centers (GC), but the mechanisms of such changes are poorly understood. Activation-induced cytidine deaminase (AID) has been recently implicated recently in DNA demethylation through its deaminase activity coupled with DNA repair. We investigated the epigenetic function of AID in vivo in germinal center B cells (GCB) isolated from wild type (WT) and AID-deficient (Aicda-/-) mice. We determined that the transit of B cells through the GC is associated with marked locus-specific loss of methylation and increased methylation diversity, both of which are lost in Aicda-/- animals. Differentially methylated cytosines (DMCs) between GCB and naïve B cells (NB) are enriched in genes that are targeted for somatic hypermutation (SHM) by AID and these genes form networks required for B cell development and proliferation. Finally, we observed significant conservation of AID-dependent epigenetic reprogramming between mouse and human B cells. ERRBS and RNA-seq of wild type and Aicda knockout murine naive and germinal center B cells. ERRBS of human naive and germinal center B cells

2015-09-15 | E-GEOD-71702 | biostudies-arrayexpress

DNA methylation signatures define molecular subtypes of Diffuse Large B Cell Lymphoma

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.

2010-08-09 | GSE23501 | GEO

DNA Methylation Dynamics of Germinal Center B Cells Are Mediated by AID

2015-09-15 | GSE71702 | GEO

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