title: Higher incidence of the SNP Met 788 Ile in the coding region of A20 in diffuse large B cell lymphomas.
abstract: Genetic alterations causing constitutive activation of the nuclear factor kappa B (NF-κB) signaling pathway has been associated with the development of lymphomas. A20 (TNFAIP3) is a key regulator of NF-κB signaling. Its suppressor functions are often inactivated by deletions and/or mutations in various hematologic malignancies. Since we recently found the rs143002189 polymorphism in the A20 loci in our multiple myeloma samples, we further investigated this polymorphism in different lymphoid neoplasias. For this purpose, we tested 479 cases of the most common B cell malignancies for the presence of the rs143002189 polymorphism. We found a significant higher occurrence of the rs143002189 polymorphism in diffuse large B cell lymphoma (DLBCL) compared to non-neoplastic controls and other types of B cell malignancies. Furthermore, structure analyses of the mutated A20 protein led to the assumption that the new steric interaction within the protein is responsible for a reduced or inactivated A20 protein. Our data indicates that in a significant fraction of patients, rs143002189 might contribute to the development of DLBCL.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz Austria, Graz, Austria.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wenzl
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz Austria, Graz, Austria.
authors.forename: Sybille
authors.initials: S
authors.lastname: Hofer
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz Austria, Graz, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Troppan
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz Austria, Graz, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Lassnig
authors.affiliation: Institute of Pathology, Medical University of Graz Austria, Graz, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Steinbauer
authors.affiliation: Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz Austria, Graz, Austria.
authors.forename: Marco
authors.initials: M
authors.lastname: Wiltgen
authors.affiliation: Division of Medical and Chemical Laboratory Diagnostics, Medical University of Graz Austria, Graz, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zulus
authors.affiliation: Division of Medical and Chemical Laboratory Diagnostics, Medical University of Graz Austria, Graz, Austria.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.affiliation: Institute of Pathology, Medical University of Graz Austria, Graz, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Beham-Schmid
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz Austria, Graz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Neumeister
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz Austria, Graz, Austria. alexander.deutsch@medunigraz.at.
authors.forename: Alexander
authors.initials: A
authors.lastname: Deutsch
mesh_terms: D016022:Case-Control Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000453:epidemiology / Q000235:genetics*; D008958:Models, Molecular; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000235:genetics*
chemical_list: C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: A20; DLBCL; Lymphoma; Polymorphism