title: Role of nuclear factor-κB regulators TNFAIP3 and CARD11 in Middle Eastern diffuse large B-cell lymphoma.
abstract: Aberrant nuclear factor-κB (NF-κB) regulation has been observed in many hematopoietic malignancies including diffuse large B-cell lymphoma (DLBCL). Considering the potential therapeutic utility of targeting NF-κB and its key modulators, we studied genetic alterations (mutations and amplifications) in TNFAIP3 and CARD11 genes in DLBCL samples. The incidence of CARD11 and TNFAIP3 mutations was 10.7% and 4.6%, respectively. Interestingly, CARD11 amplification was seen in a significant proportion of cases of DLBCL (23%) and was linked to NF-κB activation (p = 0.0142). Immunohistochemical analysis of DLBCL samples showed CARD11 overexpression and loss of TNFAIP3 in 17.7% (32/181) and 13.5% (24/178), respectively. Poor overall survival was noted in DLBCL harboring CARD11 gene amplification (p = 0.0491). Our study reports the incidence of TNFAIP3 and CARD11 alterations in Saudi DLBCL, a potentially unique ethnic group, and highlights for the first time the role of CARD11 gene amplification as a novel mechanism for NF-κB activation in Middle Eastern DLBCL.
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Rong
authors.initials: R
authors.lastname: Bu
authors.forename: Prashant
authors.initials: P
authors.lastname: Bavi
authors.forename: Jehad
authors.initials: J
authors.lastname: Abubaker
authors.forename: Zeenath
authors.initials: Z
authors.lastname: Jehan
authors.forename: Wael
authors.initials: W
authors.lastname: Al-Haqawi
authors.forename: Dahish
authors.initials: D
authors.lastname: Ajarim
authors.forename: Fouad
authors.initials: F
authors.lastname: Al-Dayel
authors.forename: Shahab
authors.initials: S
authors.lastname: Uddin
authors.forename: Khawla S
authors.initials: KS
authors.lastname: Al-Kuraya
mesh_terms: D000368:Aged; D018912:Arabs / Q000235:genetics*; D001483:Base Sequence; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006162:Guanylate Cyclase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D053468:CARD Signaling Adaptor Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C426242:CARD11 protein, human; D006162:Guanylate Cyclase