Role of microRNAs and microRNA machinery in the pathogenesis of Diffuse large B-cell Lymphomas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42906 | GEO | 2014/01/27
SECONDARY ACCESSION(S): PRJNA183858
REPOSITORIES: GEO
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Project description:We performed miRNA expression profiling in a series of de novo DLBCLs, transformed DLBCLs and non-neoplastic lymph nodes using a microarray approach. Significant differentially expressed miRNAs among groups were identified using SAM analysis. Agilent microarray platform containing 470 miRNAs was used to determine miRNA expression profiles in 45 DLBCL cases (32 de novo and 13 transformed) and 10 lymph nodes. To validate the microarray platform, the expression levels of selected miRNAs were evaluated using qRT-PCR.
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Project description:Diffuse large B-cell lymphoma (DLBCL) is a clinically and biologically heterogeneous disease. We have characterized recurrent copy number alterations (CNAs) in a large series of primary DLBCLs with HD-SNP arrays and the GISTIC algromithm. We evaluated the associations between transcript abundance and the presence of specific CNAs by obtaining RNA profiles on the majority of the primary DLBCLs and integrating the gene expression profiles with the copy number data.
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Project 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.
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