title: Deletion of the TNFAIP3/A20 gene detected by FICTION analysis in classical Hodgkin lymphoma.
abstract: BACKGROUND
  The TNFAIP3 gene, which encodes a ubiquitin-modifying enzyme (A20) involved in the negative regulation of NF-κB signaling, is frequently inactivated by gene deletions/mutations in a variety of B-cell malignancies. However, the detection of this in primary Hodgkin lymphoma (HL) specimens is hampered by the scarcity of Hodgkin Reed-Sternberg (HR-S) cells even after enrichment by micro-dissection.
  
  
  METHODS
  We used anti-CD30 immunofluorescence with fluorescence in-situ hybridization (FISH) to evaluate the relative number of TNFAIP3/CEP6 double-positive signals in CD30-positive cells.
  
  
  RESULTS
  From a total of 47 primary classical Hodgkin lymphoma (cHL) specimens, 44 were evaluable. We found that the relative numbers of TNFAIP3/CD30 cells were distributed among three groups, corresponding to those having homozygous (11%), heterozygous (32%), and no (57%) deletions in TNFAIP3. This shows that TNFAIP3 deletions could be sensitively detected using our chosen methods.
  
  
  CONCLUSIONS
  Comparing the results with mutation analysis, TNFAIP3 inactivation was shown to have escaped detection in many samples with homozygous deletions. This suggests that TNFAIP3 inactivation in primary cHL specimens might be more frequent than previously reported.
authors.affiliation: Hematology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nomoto
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Hiramoto
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kato
authors.forename: Masashi
authors.initials: M
authors.lastname: Sanada
authors.forename: Akiko Miyagi
authors.initials: AM
authors.lastname: Maeshima
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Fumie
authors.initials: F
authors.lastname: Hosoda
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Asakura
authors.forename: Wataru
authors.initials: W
authors.lastname: Munakata
authors.forename: Naohiro
authors.initials: N
authors.lastname: Sekiguchi
authors.forename: Dai
authors.initials: D
authors.lastname: Maruyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakagama
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D005838:Genotype; D006689:Hodgkin Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D017730:Ki-1 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017730:Ki-1 Antigen; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3