title: BCR and TLR signaling pathways are recurrently targeted by genetic changes in splenic marginal zone lymphomas.
abstract: The genetics and pathogenesis of splenic marginal zone lymphoma are poorly understood. The lymphoma lacks chromosome translocation, and approximately 30% of cases are featured by 7q deletion, but the gene targeted by the deletion is unknown. A recent study showed inactivation of A20, a "global" NF-κB negative regulator, in 1 of 12 splenic marginal zone lymphomas. To investigate further whether deregulation of the NF-κB pathway plays a role in the pathogenesis of splenic marginal zone lymphoma, we screened several NF-κB regulators for genetic changes by PCR and sequencing. Somatic mutations were found in A20 (6/46=13%), MYD88 (6/46=13%), CARD11 (3/34=8.8%), but not in CD79A, CD79B and ABIN1. Interestingly, these genetic changes are largely mutually exclusive from each other and MYD88 mutation was also mutually exclusive from 7q deletion. These results strongly suggest that deregulation of the TLR (toll like receptor) and BCR (B-cell receptor) signaling pathway may play an important role in the pathogenesis of splenic marginal zone lymphoma.
authors.affiliation: Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Yan
authors.forename: Yuanxue
authors.initials: Y
authors.lastname: Huang
authors.forename: A James
authors.initials: AJ
authors.lastname: Watkins
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kocialkowski
authors.forename: Naiyan
authors.initials: N
authors.lastname: Zeng
authors.forename: Rifat A
authors.initials: RA
authors.lastname: Hamoudi
authors.forename: Peter G
authors.initials: PG
authors.lastname: Isaacson
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
authors.forename: Andrew
authors.initials: A
authors.lastname: Wotherspoon
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Du
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D004268:DNA-Binding Proteins / Q000235:genetics; D006162:Guanylate Cyclase / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013160:Splenic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D053468:CARD Signaling Adaptor Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053594:Myeloid Differentiation Factor 88; D009687:Nuclear Proteins; D011947:Receptors, Antigen, B-Cell; D051193:Toll-Like Receptors; D016159:Tumor Suppressor Protein p53; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C426242:CARD11 protein, human; D006162:Guanylate Cyclase
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