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MiRNA expression profile of human MALT lymphoma compared to gastritis and gDLBCL

ABSTRACT: To obtain global miRNA expression signatures of gDLBCL and its precursor lesions, total RNA isolated from 7-8 cases each of Helicobacter-associated reactive gastritis, low grade MALT lymphoma and high grade gDLBCL was hybridized to Agilent miRNA microarrays representing 795 human mature miRNAs. Unsupervised hierarchical clustering analysis revealed a clear segregation of the gDLBCL cases from the low grade MALT lymphomas and the gastritis samples; the segregation of the latter two disease entities was only incomplete (Figure 1A), reflecting the relative biological similarity of gastritis and low grade lymphomas. Statistical analysis of the dataset revealed only 26 differentially expressed miRNAs between these two groups (p<0.05), whereas 57 miRNAs exhibited significant differences in expression between low and high grade lymphomas.

ORGANISM(S): Homo sapiens

PROVIDER: GSE24485 | GEO | 2010/10/02

SECONDARY ACCESSION(S): PRJNA132517

REPOSITORIES: GEO

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Project description:MALT lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the NF-ÎºB pathway. Gastric MALT lymphomas harboring such translocation do not respond to H. pylori eradication, while those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 24 MALT lymphomas (15 translocation-positive, 9 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-ÎºB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions showed that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-ÎºB target genes, particularly TLR6, CCR2, CD69 and BCL2, while translocation-negative cases were featured by active inflammatory and immune responses, such as IL8, CD86, CD28 and ICOS. Separate analyses of the genes differentially expressed between translocation-positive and negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10 mediated NF-ÎºB activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors. This study compares MALT with other lymphomas, namely follicular lymphomas (FL) and mantle cell lymphomas (MCL), and investigates the molecular mechanisms of the lymphomagenesis between translocation-positive versus -negative MALT lymphoma cases in order to derive the pathways leading to MALT lymphoma pathogenesis. The study uses fresh frozen tissues from 24 MALT lymphoma cases with 7 FL and 7 MCL. Samples were run on the HG-U133A, HG-U133B, and HG-U133 plus2 GeneChips.

Project description:MALT lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the NF-κB pathway. Gastric MALT lymphomas harboring such translocation do not respond to H. pylori eradication, while those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 24 MALT lymphomas (15 translocation-positive, 9 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-κB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions showed that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-κB target genes, particularly TLR6, CCR2, CD69 and BCL2, while translocation-negative cases were featured by active inflammatory and immune responses, such as IL8, CD86, CD28 and ICOS. Separate analyses of the genes differentially expressed between translocation-positive and negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10 mediated NF-κB activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors. This study compares MALT with other lymphomas namely follicular and mantle cell lymphomas, and investigates the molecular mechanisms of the lymphomagenesis between translocation positive versus negative MALT lymphoma cases in order to derive the pathways leading to MALT lymphoma pathogenesis using GSEA, GO, dynamic pathway analysis as well as other bioinformatics analysis. Samples were run on the Affymetrix HG-U133A and HG-U133 plus2 GeneChips.

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MiRNA expression profile of human MALT lymphoma compared to gastritis and gDLBCL

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