Role of nuclear factor-κB regulators TNFAIP3 and CARD11 in Middle Eastern diffuse large B-cell lymphoma

Rong Bu, Prashant Bavi, Jehad Abubaker, Zeenath Jehan, Wael Al-Haqawi, Dahish Ajarim, Fouad Al-Dayel, Shahab Uddin, Khawla S. Al-Kuraya

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9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1971-1977
Number of pages7
JournalLeukemia and Lymphoma
Volume53
Issue number10
DOIs
Publication statusPublished - 1 Oct 2012

Keywords

  • A20 (TNFAIP3)
  • CARD11
  • Deletion
  • DLBCL
  • Mutation
  • NF-κB
  • NHL therapy
  • Tissue microarray

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