title: A20 (TNFAIP3) deletion in Epstein-Barr virus-associated lymphoproliferative disorders/lymphomas.
abstract: A negative regulator of the nuclear factor (NF)-κB pathway, A20 (TNFAIP3), is inactivated in several types of lymphomas; particularly in diffuse large B-cell lymphoma (DLBCL), classical Hodgkin's lymphoma, and extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue. These findings suggest that the NF-κB activation is related to A20 inactivation. Recently, A20 inactivation has also been observed in Epstein-Barr virus (EBV)-related lymphomas; however, this occurrence has not been well investigated. Moreover, NF-κB is a key molecule in activated B-cell-like (ABC)-type DLBCL; EBV-associated DLBCL is of the ABC type. Therefore, we focused on A20 deletions in EBV-associated lymphoproliferative disorders/lymphomas. Using fluorescent in situ hybridization analysis, A20 deletions were identified in 4 of 13 samples from patients with pyothorax-associated lymphoma (PAL) (31%), 3 of 20 samples from nasal-type NK/T cell lymphomas (NKTLs) (15%), 1 of 8 samples of EBV-positive DLBCL of the elderly (DLBCL-e) (13%), but not in any of the 11 samples from individuals with methotrexate-related lymphoproliferative disorder (MTX-LPD) (0%). Among the samples with A20 deletions, EBV latent membrane protein 1 (LMP-1) expression was detected in all 4 of the PAL samples with A20 deletions and in the DLBCL-e sample with an A20 deletion, but not in any of the 3 NKTL samples. This finding indicated that A20 deletions were not directly related to the EBV latency pattern of lymphomas, although such deletions might be related to the diagnostic category. Immunohistologically, the A20 protein was absent in 2 (15%) of the 13 PAL samples, 1 (9%) of 11 MTX-LPD samples, and in none of the 20 NKTL (0%) or 8 DLBCL-e samples. In conclusion, A20 deletion and/or dysfunctional expression are frequently associated with PALs, and A20 abnormalities may be related to the pathogenesis of PAL.
authors: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors: Midori
authors: M
authors: Ando
authors: Yasuharu
authors: Y
authors: Sato
authors: Katsuyoshi
authors: K
authors: Takata
authors: Junko
authors: J
authors: Nomoto
authors: Shigeo
authors: S
authors: Nakamura
authors: Koichi
authors: K
authors: Ohshima
authors: Tamotsu
authors: T
authors: Takeuchi
authors: Yorihisa
authors: Y
authors: Orita
authors: Yukio
authors: Y
authors: Kobayashi
authors: Tadashi
authors: T
authors: Yoshino
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016724:Empyema, Pleural / Q000150:complications; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D017353:Gene Deletion; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000821:virology; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014763:Viral Matrix Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; C099537:Epstein-Barr virus encoded RNA 1; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3