TNFAIP3(A20) genetic alterations in AIDS-related lymphomas

Lisa Giulino,Susan Matthew,Gianna Ballon,Amy Chadburn,Lorenzo Leoncini,Giuseppina Antonicelli,Sharon Barouk,Wayne Tam,Ethel Cesarman

doi:10.1186/1750-9378-5-s1-a82

Abstract

Background 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 EpsteinBarr virus (EBV) infection. EBV expresses latent viral oncoproteins that constitutively activate the transcription factor NFB, 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 NFB activity, and recent reports have described mutations in regulators of NFB. One of the frequently mutated regulatory genes is TNFAIP3, which encodes A20, a ubiquitin modifying enzyme involved in the termination of NFB 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 NFB activation and the incidence of mutations in A20 have not been described.

Highlights

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
Materials and methods We evaluated archival formalin-fixed paraffin-embedded tissue samples of AIDS-related lymphoma for genetic alterations in A20
*Correspondence: giulinol@mskcc.org 1Department of Pediatrics, New York Presbyterian Hospital – Cornell, New York, NY, USA Full list of author information is available at the end of the article was prepared, and characterization of viral status and lymphoma subtype were determined by immunohistochemistry and in situ hybridization for Epstein-Barr encoded RNA (EBER)

Summary

Introduction

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. Lymphomas that are not associated with EBV can display increased NFB activity, and recent reports have described mutations in regulators of NF-B. One of the frequently mutated regulatory genes is TNFAIP3, which encodes A20, a ubiquitin modifying enzyme involved in the termination of NF-B 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].

Results

Conclusion