title: Tumor suppressor TNFAIP3 (A20) is frequently deleted in Sézary syndrome.
abstract: Despite recent therapeutic improvements, the prognosis for patients suffering from Sézary syndrome (SS), a disseminated form of cutaneous T-cell lymphomas, is still poor. We identified bi- and monoallelic deletions of the tumor necrosis factor-α-induced protein 3 gene (TNFAIP3; A20) in a high proportion of SS patients as well as biallelic A20 deletion in the SS-derived cell line SeAx. Furthermore, we demonstrate that inhibition of A20 activates the NF-κB pathway thereby increasing the proliferation of normal T lymphocytes. On the other hand, the reconstitution of A20 expression slowed down the cell cycle in SeAx cells. Recently A20 inactivation has been reported in various B-cell lymphomas. In this study, we show that A20 is also a putative tumor suppressor in the T-cell malignancy-SS.
authors.affiliation: Clinic for Internal Medicine C, University Greifswald, Greifswald, Germany.
authors.forename: F C M
authors.initials: FC
authors.lastname: Braun
authors.forename: P
authors.initials: P
authors.lastname: Grabarczyk
authors.forename: M
authors.initials: M
authors.lastname: Möbs
authors.forename: F K
authors.initials: FK
authors.lastname: Braun
authors.forename: J
authors.initials: J
authors.lastname: Eberle
authors.forename: M
authors.initials: M
authors.lastname: Beyer
authors.forename: W
authors.initials: W
authors.lastname: Sterry
authors.forename: F
authors.initials: F
authors.lastname: Busse
authors.forename: J
authors.initials: J
authors.lastname: Schröder
authors.forename: M
authors.initials: M
authors.lastname: Delin
authors.forename: G K
authors.initials: GK
authors.lastname: Przybylski
authors.forename: C A
authors.initials: CA
authors.lastname: Schmidt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002453:Cell Cycle; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012751:Sezary Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3