Document Detail


Constitutive expression of the AP-1 transcription factors c-jun, junD, junB, and c-fos and the marginal zone B-cell transcription factor Notch2 in splenic marginal zone lymphoma.
MedLine Citation:
PMID:  15507668     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Splenic marginal zone lymphoma (SMZL) is a lymphoma type of putative marginal zone B-cell origin. No specific genetic alterations have yet been demonstrated in SMZL. Clinically, SMZL is a low-grade B-cell non-Hodgkin lymphoma. However, the presence of p53 mutation, 7q22-7q32 deletion or the absence of somatic hypermutations of immunoglobulin genes has been correlated with a worse prognosis. In this study, we analyzed genome-wide gene expression of 24 cases of SMZL using the microarray technique. The AP-1 transcription factors c-jun, junD, junB, and c-fos as well as Notch2 were found to be specifically up-regulated. These data were confirmed by real-time PCR and immunohistochemical staining of tissue sections. The absence of concordant high expression of the MAP kinases, the signaling cascade leading to AP-1 up-regulation, suggests autoregulation of the AP-1 transcription factors and an important role in SMZL oncogenesis. High expression of Notch2, a transcription factor that induces marginal zone B-cell differentiation, is highly suggestive for a marginal zone B-cell origin of SMZL. In addition, SMZL with the 7q deletion showed high expression of TGF-beta1 and low expression of the DNA helicase XPB, a crucial part of the nucleotide excision repair complex, possibly explaining the more aggressive clinical course of those cases.
Authors:
Gunhild Trøen; Vigdis Nygaard; Tor-Kristian Jenssen; Ida Münster Ikonomou; Anne Tierens; Estella Matutes; Alicja Gruszka-Westwood; Daniel Catovsky; Ola Myklebost; Grete Lauritzsen; Eivind Hovig; Jan Delabie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of molecular diagnostics : JMD     Volume:  6     ISSN:  1525-1578     ISO Abbreviation:  J Mol Diagn     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-27     Completed Date:  2005-04-22     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  100893612     Medline TA:  J Mol Diagn     Country:  United States    
Other Details:
Languages:  eng     Pagination:  297-307     Citation Subset:  IM    
Affiliation:
Department of Pathology, The Norwegian Radium Hospital, University of Oslo, Montebello N-0310, Oslo, Norway. gunhild.troen@labmed.uio.no.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Chromosomes, Human, Pair 7
DNA / metabolism
Down-Regulation
Fluorescent Dyes / pharmacology
Gene Deletion
Gene Expression Regulation, Neoplastic*
Genes, jun / genetics*
Genes, p53
Humans
Immunohistochemistry
Lymphoma, B-Cell / metabolism*
Microsatellite Repeats
Mutation
Nucleic Acid Hybridization
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Prognosis
Proto-Oncogene Proteins c-fos / biosynthesis*
Proto-Oncogene Proteins c-jun / biosynthesis*
Receptor, Notch2
Receptors, Cell Surface / biosynthesis*
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factor AP-1 / biosynthesis*
Transcription, Genetic
Up-Regulation
Chemical
Reg. No./Substance:
0/Fluorescent Dyes; 0/NOTCH2 protein, human; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Receptor, Notch2; 0/Receptors, Cell Surface; 0/Transcription Factor AP-1; 9007-49-2/DNA
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