Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling and genotyping of 26 human mantle cell lymphoma samples

ABSTRACT: Among B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. Among the transcripts with high correlation between DNA and RNA, we identified SYK, a tyrosine kinase involved in B-cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo-1 cell line. Low-level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas.

ORGANISM(S): Homo sapiens

SUBMITTER: Francesco Bertoni

PROVIDER: E-GEOD-4176 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma.

Rinaldi Andrea A Kwee Ivo I Taborelli Monica M Largo Cristina C Uccella Silvia S Martin Vittoria V Poretti Giulia G Gaidano Gianluca G Calabrese Giuseppe G Martinelli Giovanni G Baldini Luca L Pruneri Giancarlo G Capella Carlo C Zucca Emanuele E Cotter Finbarr E FE Cigudosa Juan C JC Catapano Carlo V CV Tibiletti Maria G MG Bertoni Francesco F

British journal of haematology 20060201 3

Among B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. ...[more]

PMID: 16409295

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Project description:Microarray technology provides a powerful tool for gene discovery studies, but the development of microarrays for individual species can be expensive and time-consuming. In this study, we test the suitability of a Danio rerio oligonucleotide microarray for application in a species with few genomic resources, the coral reef fish Pomacentrus moluccensis. Coral reef fishes are expected to experience rising sea surface temperatures due to climate change. How well tropical reef fish species will respond to these increased temperatures and which genes are important for resistance and adaptation to elevated temperatures is not known. Microarray technology may help identify candidate genes for thermal stress resistance in coral reef fishes. Results from a comparative genomic DNA hybridisation experiment and direct sequence comparisons indicate that for most genes there is significant sequence similarity between P. moluccensis and D. rerio, suggesting that the D. rerio array is applicable to P. moluccensis. Heterologous microarray experiments on heat-stressed P. moluccensis identified changes in transcript abundance at 120 gene loci, with many genes involved in protein processing, transcription, and cell growth. Changes in transcript abundance for a selection of candidate genes were confirmed by quantitative real-time PCR. We have demonstrated that heterologous microarrays can be successfully employed to study non-model organisms. Such a strategy thus greatly enhances the applicability of microarray technology to the field of environmental and functional genomics and will be useful for investigating the molecular basis of thermal adaptation in coral reef fishes. Keywords: stress response, comparative genomic hybridization (CGH) Common reference design [Stress response_P. moluccensis]: four individual treatment fish (heat-stressed) are contrasted in four microarray hybridisations against a pooled control consisting of four fish kept at ambient temperature. All eight fish employed in this analysis were wild-captured and are biological replicates. The experiment included dye-swap, i.e. stressed fish were labelled red in two hybridisations and green in the other two hybridisations. Common reference design [CGH_P. moluccensis and D. rerio]: four individual P. moluccensis gDNA samples are contrasted in four microarray hybridisations against a pooled gDNA sample consisting of three D. rerio. The experiment included dye-swaps.

Dataset Information

Transcription profiling and genotyping of 26 human mantle cell lymphoma samples

Publications

Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma.

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