title: Nodal marginal zone lymphoma: gene expression and miRNA profiling identify diagnostic markers and potential therapeutic targets.
abstract: 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 NMZL cases. For comparison, 16 follicular lymphomas (FLs), 9 extranodal marginal zone lymphomas, and 8 reactive lymph nodes and B-cell subtypes were included. The results were validated by quantitative RT-PCR in an independent series, including 61 paraffin-embedded NMZLs. NMZL signature showed an enriched expression of gene sets identifying interleukins, integrins, CD40, PI3K, NF-κB, and TGF-β, 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 G(2)/M and germinal center were down-regulated. Comparison of the gene expression profiles of NMZL and FL showed enriched expression of CHIT1, TGFB1, and TACI in NMZL, and BCL6, LMO2, and CD10 in FL. NMZL displayed increased expression of miR-221, miR-223, and let-7f, whereas FL strongly expressed miR-494. Our study identifies new candidate diagnostic molecules for NMZL and reveals survival pathways activated in NMZL.
authors: Virgen de la Salud Hospital, Toledo, Spain.
authors: Alberto J
authors: AJ
authors: Arribas
authors: Yolanda
authors: Y
authors: Campos-Martín
authors: Cristina
authors: C
authors: Gómez-Abad
authors: Patrocinio
authors: P
authors: Algara
authors: Margarita
authors: M
authors: Sánchez-Beato
authors: Maria S
authors: MS
authors: Rodriguez-Pinilla
authors: Santiago
authors: S
authors: Montes-Moreno
authors: Nerea
authors: N
authors: Martinez
authors: Javier
authors: J
authors: Alves-Ferreira
authors: Miguel A
authors: MA
authors: Piris
authors: Manuela
authors: M
authors: Mollejo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D018442:Lymphoma, B-Cell, Marginal Zone / Q000175:diagnosis / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger