Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis

Splenic marginal zone lymphoma (SMZL) is a newly recognized lymphoma type whose precise molecular pathogenesis is still essentially unknown. This hampers differential diagnosis with other small B-cell malignancies. With the aim of characterizing this tumor more comprehensively, and of identifying ne...

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Bibliographic Details
Published in:Blood 2005-09, Vol.106 (5), p.1831-1838
Main Authors: Ruiz-Ballesteros, Elena, Mollejo, Manuela, Rodriguez, Antonia, Camacho, Francisca I., Algara, Patrocinio, Martinez, Nerea, Pollán, Marina, Sanchez-Aguilera, Abel, Menarguez, Javier, Campo, Elias, Martinez, Pedro, Mateo, Marisol, Piris, Miguel A.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Biomarkers, Tumor - analysis
Germ-Line Mutation
Hematologic and hematopoietic diseases
Humans
Immunoglobulin Heavy Chains - genetics
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lymphoma - diagnosis
Lymphoma - genetics
Lymphoma - metabolism
Medical sciences
NF-kappa B - genetics
NF-kappa B - metabolism
Oligonucleotide Array Sequence Analysis - methods
Phylogeny
Prognosis
Receptors, Antigen, B-Cell - genetics
Receptors, Antigen, B-Cell - metabolism
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction - physiology
Splenic Neoplasms - diagnosis
Splenic Neoplasms - genetics
Splenic Neoplasms - metabolism
Time Factors
Tissue Array Analysis - methods
Treatment Outcome
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
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Summary:Splenic marginal zone lymphoma (SMZL) is a newly recognized lymphoma type whose precise molecular pathogenesis is still essentially unknown. This hampers differential diagnosis with other small B-cell malignancies. With the aim of characterizing this tumor more comprehensively, and of identifying new diagnostic and prognostic markers, we performed cDNA microarray expression profiling and tissue microarray (TMA) immunohistochemical studies in a relatively large series of 44 SMZLs. The results were related to immunoglobulin heavy chain variable region (IgVH) mutational status and clinical outcome. SMZLs display a largely homogenous signature, implying the existence of a single molecular entity. Of the genes deregulated in SMZLs, special mention may be made of the genes involved in B-cell receptor (BCR) signaling, tumor necrosis factor (TNF) signaling and nuclear factor-κB (NF-κB) activation, such as SYK, BTK, BIRC3, TRAF3, and LTB. Other genes observed were SELL and LPXN, which were highly expressed in spleen, and lymphoma oncogenes, such as ARHH and TCL1. In contrast, the genes CAV1, CAV2, and GNG11 located in 7q31, a commonly deleted area, were down-regulated in the entire series. A comparison with the genes comprising the signature of other small B-cell lymphomas identified 3 genes whose expression distinguishes SMZL, namely ILF1, SENATAXIN, and CD40. Shorter survival was associated with CD38 expression, naive IgVH genes, and the expression of a set of NF-κB pathway genes, including TRAF5, REL, and PKCA. (Blood. 2005;106:1831-1838)
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2004-10-3898