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| 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
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|
| 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
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| |
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| 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 |
| E-mail(s) |
francesco.bertoni@irb.unisi.ch, andrea.rinaldi@unisi.irb.ch
|
| 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)
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| Relations |
| BioProject |
PRJNA94977 |
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