title: A20 (TNFAIP3) genetic alterations in EBV-associated AIDS-related lymphoma.
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.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Giulino
authors.forename: Susan
authors.initials: S
authors.lastname: Mathew
authors.forename: Gianna
authors.initials: G
authors.lastname: Ballon
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Sharon
authors.initials: S
authors.lastname: Barouk
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Antonicelli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leoncini
authors.forename: Yi Fang
authors.initials: YF
authors.lastname: Liu
authors.forename: Swarna
authors.initials: S
authors.lastname: Gogineni
authors.forename: Wayne
authors.initials: W
authors.lastname: Tam
authors.forename: Ethel
authors.initials: E
authors.lastname: Cesarman
mesh_terms: D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016483:Lymphoma, AIDS-Related / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014763:Viral Matrix Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D014763:Viral Matrix Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3