A20 (TNFAIP3) genetic alterations in EBV-associated AIDS-related lymphoma

Blood. 2011 May 5;117(18):4852-4. doi: 10.1182/blood-2010-10-310995. Epub 2011 Mar 15.

Abstract

A20, a negative regulator of NF-κB, has been implicated as a tumor suppressor gene in multiple types of B-cell lymphoma. AIDS-related lymphomas (ARLs) are high-grade B-cell lymphomas that are frequently associated with EBV infection. We examined a panel of ARLs for A20 alterations. FISH showed A20 deletion in 6 of 33 cases (18%). A20 mutations were found in 3 of 19 cases (16%), including 2 cases with deletions of the comple-mentary allele. Immunohistochemistry showed the absence of A20 protein in 7 of 55 samples (13%). In contrast to reports in Hodgkin lymphoma in which EBV infection and A20 alteration are mutually exclusive, A20 inactivation was observed in both EBV(+) and EBV(-) cases. The EBV latent membrane protein 1, which activates NF-κB, was not expressed in 12 of 13 cases with A20 loss. In ARLs loss of A20 may be an alternative mechanism of NF-κB activation in the absence of latent membrane protein 1 expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Mutational Analysis
  • DNA-Binding Proteins
  • Epstein-Barr Virus Infections / genetics*
  • Epstein-Barr Virus Infections / metabolism
  • Gene Deletion
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lymphoma, AIDS-Related / genetics*
  • Lymphoma, AIDS-Related / metabolism
  • Lymphoma, AIDS-Related / virology*
  • Mutation*
  • NF-kappa B / metabolism
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Viral Matrix Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Nuclear Proteins
  • Viral Matrix Proteins
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3