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Series GSE25527 Query DataSets for GSE25527
Status Public on Jan 30, 2011
Title Cleavage of NIK by the API2-MALT1 Fusion Oncoprotein Leads to Noncanonical NF-{kappa}B Activation
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Proper regulation of nuclear factor κB (NF-κB) transcriptional activity is required for normal lymphocyte function, and deregulated NF-κB signaling can facilitate lymphomagenesis. We demonstrate that the API2-MALT1 fusion oncoprotein created by the recurrent t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma induces proteolytic cleavage of NF-κB–inducing kinase (NIK) at arginine 325. NIK cleavage requires the concerted actions of both fusion partners and generates a C-terminal NIK fragment that retains kinase activity and is resistant to proteasomal degradation. The resulting deregulated NIK activity is associated with constitutive noncanonical NF-κB signaling, enhanced B cell adhesion, and apoptosis resistance. Our study reveals the gain-of-function proteolytic activity of a fusion oncoprotein and highlights the importance of the noncanonical NF-κB pathway in B lymphoproliferative disease.
 
Overall design This study compares nine t(11;18)-positive MALT lymphomas (8 from the stomach and 1 from lung) and eight translocation negative MALT lymphomas (all from the stomach) using gene set enrichment analysis (GSEA). All cases were subjected to Affymetrix U133A and U133B microarray analysis. The cases used in this study are the same cases used for the study by Hamoudi et al. (2010) entitled "Differential expression of NF-kB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism" with GEO reference number: GSE18736

and

PubMed ID: http://www.ncbi.nlm.nih.gov/pubmed/20520640

All cases were subjected to non-specific filtering to eliminate non-variant probes, then the U133A and U133B probes were collapsed and the collapsed set was subjected to GSEA using the NF-kB target gene set as described in Hamoudi et al. (2010) study mentioned above.

The 34 samples in this study are identical to the ones done in the previous series except that the gene set enrichment was done on just those 34 samples and not the complete set.
 
Contributor(s) Rosebeck S, Madden L, Jin X, Gu S, Appert A, Hamoudi R, Noels H, Sagaert X, Van Loo P, Baens M, Du M, Lucas PC, McAllister-Lucas LM
Citation(s) 21273489
Submission date Nov 22, 2010
Last update date Aug 10, 2018
Contact name Rifat Hamoudi
E-mail(s) [email protected]
Organization name University College London
Department Surgery
Lab Charles Bell House
Street address 67-73 Riding House Street
City London
ZIP/Postal code W1W 7EJ
Country United Kingdom
 
Platforms (2)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
GPL97 [HG-U133B] Affymetrix Human Genome U133B Array
Samples (34)
GSM346939 MALT_Lymphoma_t(11;18)/API2-MALT1_5
GSM346967 MALT_Lymphoma_t(11;18)/API2-MALT1_6
GSM347029 MALT_Lymphoma_t(11;18)/API2-MALT1_7
Relations
BioProject PRJNA133997

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE25527_RAW.tar 92.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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