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.

Keywords::

• DLBCL
• A20 (TNFAIP3)
• CARD11
• mutation
• deletion
• NF-κB
• NHL therapy
• tissue microarray

Acknowledgements

We would like to thank Zeeshan Qadri and Thara George for clinical data analysis, and Dr Sarita Prabahakaran and Valorie Balde for their technical assistance.

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.