title: Mutation analysis of tumor necrosis factor alpha-induced protein 3 gene in Hodgkin lymphoma.
abstract: OBJECTIVE
  Survival and proliferation of Hodgkin and Reed-Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (CHL), are dependent on constitutive activation of nuclear factor kB (NF-κB). A20, encoded by TNF alpha-induced protein 3 (TNFAIP3), one of the inhibitors of NF-kB, was found to be inactivated by deletions and/or point mutations in CHL.
  
  
  METHODS
  TNFAIP3mutations were examined in 37 patients with CHL by using PCR and direct sequencing. In addition, protein expression of A20 was evaluated by immunohistochemistry. Epstein-Barr virus (EBV) status of HL samples was determined by EBV EBER chromogenic in situ hybridization (ISH).
  
  
  RESULTS
  We identified 8 mutation positive cases in a collective of 37 investigated cases (22%). Mutations were most frequent in the nodular sclerosis subtype. Our results revealed the tendency that cases harboring A20 mutations were negative for A20 staining. None of A20 mutation-positive CHL cases showed EBV infection.
  
  
  CONCLUSIONS
  Our study confirms the involvement of the TNFAIP3tumor suppressor gene in CHL. A20 may represent a suppressor of human lymphoma and provide a critical molecular link between chronic inflammation and cancer. None of A20 mutation-positive CHL cases showed EBV infection. This fact suggests complementing functions of TNFAIP3inactivation and EBV infection in CHL pathogenesis and may represent an interesting point of further investigations.
authors.affiliation: Institute of Pathology, Jena University Hospital, Jena, Germany.
authors.forename: Barbara-Magdalena
authors.initials: BM
authors.lastname: Etzel
authors.affiliation: Institute of Pathology, Jena University Hospital, Jena, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Gerth
authors.affiliation: Institute of Pathology, Jena University Hospital, Jena, Germany.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Pathology, Jena University Hospital, Jena, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Wünsche
authors.affiliation: Institute of Pathology, Jena University Hospital, Jena, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Facklam
authors.affiliation: Children's Clinic, Department of Pediatric Hematology and Oncology, Jena University Hospital, Jena, Germany.
authors.forename: James F
authors.initials: JF
authors.lastname: Beck
authors.affiliation: Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany.
authors.forename: Orlando
authors.initials: O
authors.lastname: Guntinas-Lichius
authors.affiliation: Institute of Pathology, Jena University Hospital, Jena, Germany. Electronic address: Iver.Petersen@med.uni-jena.de.
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000378:metabolism* / Q000473:pathology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: A20; Hodgkin lymphoma; Mutation analysis; NF-κB signaling; TNFAIP(3)