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.
MeSH terms
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Aged
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Arabs / genetics*
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Base Sequence
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CARD Signaling Adaptor Proteins / genetics*
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CARD Signaling Adaptor Proteins / metabolism
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Female
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Gene Dosage
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Gene Expression Regulation, Neoplastic
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Guanylate Cyclase / genetics*
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Guanylate Cyclase / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins / genetics*
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Intracellular Signaling Peptides and Proteins / metabolism
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Lymphoma, Large B-Cell, Diffuse / genetics*
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Lymphoma, Large B-Cell, Diffuse / metabolism
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Lymphoma, Large B-Cell, Diffuse / mortality
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Lymphoma, Large B-Cell, Diffuse / pathology
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Male
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Middle Aged
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Mutation
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NF-kappa B / metabolism
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Neoplasm Staging
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Prognosis
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Tumor Necrosis Factor alpha-Induced Protein 3
Substances
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CARD Signaling Adaptor Proteins
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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NF-kappa B
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Nuclear Proteins
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TNFAIP3 protein, human
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Tumor Necrosis Factor alpha-Induced Protein 3
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CARD11 protein, human
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Guanylate Cyclase