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TNFAIP3(A20) genetic alterations in AIDS-related lymphomas

  • 1, 2Email author,
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Infectious Agents and Cancer20105 (Suppl 1) :A82

  • Published:


  • Lymphoma
  • Burkitt Lymphoma
  • Marginal Zone Lymphoma
  • Viral Oncoproteins
  • Weill Cornell Medical College


AIDS-related lymphomas (ARLs), which include Burkitt lymphoma and diffuse large B cell lymphoma (DLBCL), are a heterogeneous group of lymphoproliferative disorders that occur in the setting of HIV-mediated immune suppression. A subset of cases are associated with Epstein-Barr virus (EBV) infection. EBV expresses latent viral oncoproteins that constitutively activate the transcription factor NF-κB, a potent inducer of genes involved in promoting B cell survival and proliferation [1].

In immunocompetent individuals, lymphomas that are not associated with EBV can also display increased NF-κB activity, and recent reports have described mutations in regulators of NF-κB. One of the frequently mutated regulatory genes is TNFAIP3, which encodes A20, a ubiquitin modifying enzyme involved in the termination of NF-κB signaling. Mutations resulting in the inactivation of A20 have been found in a significant proportion of marginal zone lymphomas [2], classical Hodgkin’s lymphomas and primary mediastinal B cell lymphomas [3], and DLBCLs [4]. In ARL the role of NF-κB activation and the incidence of mutations in A20 have not been described.

Materials and methods

We evaluated archival formalin-fixed paraffin-embedded tissue samples of AIDS-related lymphoma for genetic alterations in A20. Tissue was collected through an international collaboration between Weill Cornell Medical College in New York, NY, and Siena University in Siena, Italy. A tissue microarray with 48 cases of ARL was prepared, and characterization of viral status and lymphoma subtype were determined by immunohistochemistry and in situ hybridization for Epstein-Barr encoded RNA (EBER). Fluorescent in situ hybridization (FISH) was used to evaluate for genomic deletions in A20, and translocations of cMYC, BCL-2, and BCL-6. Direct sequencing of the coding region of A20 was performed to evaluate for additional mutations.


FISH was performed on 48 cases of ARL. Of 21 cases with successful hybridization loss of heterozygosity at the A20 locus was observed in 6 cases (28%). Cases with A20 deletion included three diffuse large B cell lymphomas, two Burkitt lymphomas, and one Burkitt-like lymphoma. Two cases were positive for EBER but all were negative for latent membrane protein-1 (LMP-1). Partial sequencing of approximately 70% of the A20 coding regions in 23 cases did not reveal additional mutations.


A20 may represent a tumor suppressor gene in a subset of AIDS-related lymphomas. Inactivation of A20 may be an alternative mechanism of NF-κB upregulation in the absence of LMP-1.



This article has been published as part of Infectious Agents and Cancer Volume 5 Supplement 1, 2010: Proceedings of the 12th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI).The full contents of the supplement are available online at

Authors’ Affiliations

Department of Pediatrics, New York Presbyterian Hospital – Cornell, New York, NY, USA
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Department of Pathology, Weill Cornell Medical College, New York, NY, USA
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA


  1. Keller SA, Hernandez-Hopkins D, Vider J, Ponomarev V, Hyjek E, Schattner EJ, Cesarman E: NF-kappaB is essential for the progression of KSHV- and EBV-infected lymphomas in vivo. Blood. 2006, 107 (8): 3295-3302. 10.1182/blood-2005-07-2730.PubMed CentralView ArticlePubMedGoogle Scholar
  2. Novak U, Rinaldi A, Kwee I, Nandula SV, Rancoita PM, Compagno M, Cerri M, Rossi D, Murty VV, Zucca E: The NF-{kappa}B negative regulator TNFAIP3 (A20) is inactivated by somatic mutations and genomic deletions in marginal zone lymphomas. Blood. 2009, 113 (20): 4918-4921. 10.1182/blood-2008-08-174110.PubMed CentralView ArticlePubMedGoogle Scholar
  3. Schmitz R, Hansmann ML, Bohle V, Martin-Subero JI, Hartmann S, Mechtersheimer G, Klapper W, Vater I, Giefing M, Gesk S: TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J Exp Med. 2009, 206 (5): 981-989. 10.1084/jem.20090528.PubMed CentralView ArticlePubMedGoogle Scholar
  4. Compagno M, Lim WK, Grunn A, Nandula SV, Brahmachary M, Shen Q, Bertoni F, Ponzoni M, Scandurra M, Califano A: Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature. 2009, 459 (7247): 717-721. 10.1038/nature07968.PubMed CentralView ArticlePubMedGoogle Scholar


© Giulino et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.