Project description:This SuperSeries is composed of the following subset Series: GSE21846: Transcriptional profiling of 29 cases of diffuse large B cell lymphoma GSE21847: miRNA profiling of 29 cases of diffuse large B cell lymphoma GSE21848: miRNA profiling of 36 cases of diffuse large B cell lymphoma Refer to individual Series
Project description:This SuperSeries is composed of the following subset Series: GSE30357: Chip-chip from human diffuse large B cell lymphoma cell lines with IRF8 GSE30358: Mouse B cell lymphoma cell lines:IRF8 knockdown cells vs. Control GSE30519: Chip-chip from mouse diffuse large B cell lymphoma cell lines with IRF8 GSE30520: Chip-chip from mouse diffuse large B cell lymphoma cell lines with PU.1 Refer to individual Series
Project 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. Experiment Overall Design: 220 diffuse large B-cell lymphoma and Burkitt lymphoma samples hybridized to 221 HGU133A Affymetrix GeneChips
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
Project description:Large cell lymphomas of the gastrointestinal tract are currently regarded as diffuse large B-cell lymphomas despite a more favourable clinical outcome and a lower aggressiveness compared to other nodal and extranodal DLBCL. We compared gene expression profiles of 28 gastrointestinal marginal zone B-cell lymphomas and variants with several other B-cell lymphoma entities such as Burkitt’s lymphoma, nodal DLBCL, follicular lymphoma, mantle cell lymphoma, primary mediastinal B-cell lymphoma and normal B-cell populations. Based on a subset of NF-kappaB target genes, partitioning and hierarchical cluster algorithms were used which led to comparable results. The different B-cell subsets, the Burkitt’s lymphoma, and the small cell lymphomas formed distinct groups, respectively. The DLBCL were subdivided into one group containing only DLBCL samples, one subset clustered together with the PMBL samples, and another one together with the blastic variants of MZBL. These results implicate that extranodal blastic MZBL represent a distinct subgroup of DLBCL.