title: Recurrent alterations of TNFAIP3 (A20) in T-cell large granular lymphocytic leukemia.
abstract: The pathogenesis of T-cell large granular lymphocytic leukemia (T-LGL) is poorly understood, as STAT3 mutations are the only known frequent genetic lesions. Here, we identified non-synonymous alterations in the TNFAIP3 tumor suppressor gene in 3 of 39 T-LGL. In two cases these were somatic mutations, in one case the somatic origin was likely. A further case harbored a SNP that is a known risk allele for autoimmune diseases and B cell lymphomas. Thus, TNFAIP3 mutations represent recurrent genetic lesions in T-LGL that affect about 8% of cases, likely contributing to deregulated NF-κB activity in this leukemia.
authors.affiliation: Department of Haematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.|Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Johansson
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Bergmann
authors.affiliation: Genome Informatics, Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Rahmann
authors.affiliation: Genome Informatics, Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Inken
authors.initials: I
authors.lastname: Wohlers
authors.affiliation: Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Scholtysik
authors.affiliation: Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Przekopowitz
authors.affiliation: Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Seifert
authors.affiliation: Laboratory for Molecular Biology and Tumor Cytogenetics, Department of Haematology and Oncology, Linz, Austria.
authors.forename: Gertraud
authors.initials: G
authors.lastname: Tschurtschenthaler
authors.affiliation: Laboratory for Molecular Biology and Tumor Cytogenetics, Department of Haematology and Oncology, Linz, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Webersinke
authors.affiliation: Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jäger
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.affiliation: Department of Haematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.affiliation: Department of Haematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.affiliation: Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D015331:Cohort Studies; D056915:DNA Copy Number Variations; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D014644:Genetic Variation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D054066:Leukemia, Large Granular Lymphocytic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D050796:STAT3 Transcription Factor / Q000235:genetics; D017422:Sequence Analysis, DNA; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: NF-κB; STAT3; T-LGL; TNFAIP3; tumor suppressor gene