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Series GSE4176 Query DataSets for GSE4176
Status Public on Feb 08, 2006
Title Genomic and expression profiling identifies Syk as a possible therapeutic target in mantle cell lymphoma
Organism Homo sapiens
Experiment type Expression profiling by array
Genome variation profiling by SNP array
SNP genotyping by SNP array
Summary 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.
Keywords: cell type comparison
Overall design Expression profiling: Four untreated human cell lines were analyzed. No replications except for REC.
Genomic profiling: 26 MCL samples (22 patients, 4 cell lines) were analyzed. No replications except for REC
Contributor(s) Rinaldi A, Bertoni F, Kwee I
Citation(s) 16409295
Submission date Feb 03, 2006
Last update date Aug 10, 2018
Contact name Francesco Bertoni
Phone 0041918200367
Fax 0041918200397
Organization name Institute of Southern Switzerland
Department Experimental Oncology
Lab Functional Genomics
Street address Via Vela 6
City Bellinzona
State/province Ticino
ZIP/Postal code 6500
Country Switzerland
Platforms (3)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
GPL97 [HG-U133B] Affymetrix Human Genome U133B Array
GPL1266 [Mapping10K_Xba131] Affymetrix Human Mapping 10K SNP Array
Samples (36)
GSM95562 GRANTA-519 133A
GSM95563 JEKO-1 133A
GSM95564 NCEB-1 133A
BioProject PRJNA94977

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Supplementary file Size Download File type/resource
GSE4176_RAW.tar 31.5 Mb (http)(custom) TAR (of CEL)

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