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 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 (IgV(H)) 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-kappaB (NF-kappaB) 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 IgV(H) genes, and the expression of a set of NF-kappaB pathway genes, including TRAF5, REL, and PKCA.
Ruiz-Ballesteros
Elena
E
Molecular Pathology Program, Centro Nacional de Investigaciones Oncológicas, C/Melchor Fernández Almagro 3, E-28 029 Madrid, Spain.
Mollejo
Manuela
M
Rodriguez
Antonia
A
Camacho
Francisca I
FI
Algara
Patrocinio
P
Martinez
Nerea
N
Pollán
Marina
M
Sanchez-Aguilera
Abel
A
Menarguez
Javier
J
Campo
Elias
E
Martinez
Pedro
P
Mateo
Marisol
M
Piris
Miguel A
MA
D014408:Biomarkers, Tumor / Q000032:analysis*; D018095:Germ-Line Mutation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008223:Lymphoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010802:Phylogeny; D011379:Prognosis; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013160:Splenic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D046888:Tissue Array Analysis / Q000379:methods*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D014409:Tumor Necrosis Factor-alpha