title: t(11;14)(q23;q32) involving IGH and DDX6 in nodal marginal zone lymphoma.
abstract: Nodal marginal zone lymphoma (NMZL) is a primary nodal B-cell lymphoma that shares morphological and immunophenotypic characteristics with extranodal and splenic marginal zone lymphoma. Data on altered genes and signaling pathways are scarce in this rare tumor entity. To gain further insights into the genetic background of NMZL, seven cases were investigated by microarray analysis, G-banding, and FISH. Chromosomal imbalances were observed in 3/7 cases (43%) with gains of chromosome arms 1q, 8q, and 12q being the most frequent findings. Furthermore, we identified a translocation t(11;14)(q23;q32) involving IGH and DDX6. Chromosomal walking, expression analysis, siRNA-mediated gene knockdown and a yeast two hybrid screen were performed for further characterization of the translocation in vitro. In siRNA experiments, DDX6 appeared not to be involved in NF-κB activation as frequently observed for genes promoting lymphomagenesis but was found to interfere with the expression of BCL6 and BCL2 in an NF-κB independent manner. In conclusion, we identified several unbalanced aberrations and a t(11;14) involving IGH and DDX6 providing evidence for a contribution of DDX6 to lymphomagenesis by deregulation of BCL6 in NMZL.
authors.affiliation: Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Stary
authors.forename: Ursula
authors.initials: U
authors.lastname: Vinatzer
authors.forename: Leonhard
authors.initials: L
authors.lastname: Müllauer
authors.forename: Markus
authors.initials: M
authors.lastname: Raderer
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.forename: Berthold
authors.initials: B
authors.lastname: Streubel
mesh_terms: D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D020732:Cytogenetic Analysis; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D056915:DNA Copy Number Variations; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D019656:Loss of Heterozygosity; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D015398:Signal Transduction / Q000235:genetics; D014178:Translocation, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases