Nodal marginal zone lymphoma (NMZL) is a small B cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B cell lymphomas is hampered by the lack of specific markers. We have analyzed gene expression, miRNA profile and copy number data from 15 NMZLs. For comparison, 16 follicular lymphomas, 9 extranodal marginal zone lymphomas, 8 reactive lymph nodes and B cell subtypes were included. The results were validated by qRT-PCR in an independent paraffin-embedded series including 61 NMZLs. NMZL signature showed an enriched expression of gene sets identifying interleukins, integrins, CD40, PI3K, NFkB and TGF-Beta; and included genes expressed by normal marginal zone cells and memory B cells. The most highly overexpressed genes were SYK, TACI, CD74, CD82 and CDC42EP5. Genes linked to G2/M and germinal center were downregulated. Comparison of the gene expression profiles of NMZL and FL showed enriched expression of CHIT1 and TACI in NMZL, and BCL6, LMO2 and CD10 in FL. NMZL displayed increased expression of miR-223 and let-7f, while FL strongly expressed miR-494. Our study identifies new candidate diagnostic molecules for NMZL and reveals survival pathways activated in NMZL.
Overall design
microRNA-expression profiling was conducted in a series of 40 B-cell non-Hodgkin lymphoma patients (NMZL, and FL). Six lymph nodes with reactive lymphoid hyperplasia (RLN) were used as controls
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