title: Frequent down regulation of the tumor suppressor gene a20 in multiple myeloma.
abstract: Multiple myeloma (MM) is a malignant clonal expansion of plasma cells in the bone marrow and belongs to the mature B-cell neoplams. The pathogenesis of MM is associated with constitutive NF-κB activation. However, genetic alterations causing constitutive NF-κB activation are still incompletely understood. Since A20 (TNFAIP3) is a suppressor of the NF-κB pathway and is frequently inactivated in various lymphoid malignancies, we investigated the genetic and epigenetic properties of A20 in MM. In total, of 46 patient specimens analyzed, 3 single base pair exchanges, 2 synonymous mutations and one missense mutation were detected by direct sequencing. Gene copy number analysis revealed a reduced A20 gene copy number in 8 of 45 (17.7%) patients. Furthermore, immunohistochemical staining confirmed that A20 expression correlates with the reduction of A20 gene copy number. These data suggest that A20 contributes to tumor formation in a significant fraction of myeloma patients.
authors: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Katharina
authors: K
authors: Troppan
authors: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Sybille
authors: S
authors: Hofer
authors: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Kerstin
authors: K
authors: Wenzl
authors: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Markus
authors: M
authors: Lassnig
authors: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Beata
authors: B
authors: Pursche
authors: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors: Elisabeth
authors: E
authors: Steinbauer
authors: Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
authors: Marco
authors: M
authors: Wiltgen
authors: Division of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors: Barbara
authors: B
authors: Zulus
authors: Division of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors: Wilfried
authors: W
authors: Renner
authors: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors: Christine
authors: C
authors: Beham-Schmid
authors: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Alexander
authors: A
authors: Deutsch
authors: Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Peter
authors: P
authors: Neumeister
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense; D016328:NF-kappa B / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3