Mutation analysis of the TNFAIP3 (A20) tumor suppressor gene in CLL.
Chronic lymphocytic leukemia (CLL) cells show constitutive nuclear factor kappa B (NF-κB) activation, which may have a pathogenetic role. The mechanisms causing this NF-κB activity are poorly understood. A20, encoded by the TNFAIP3 gene, is a repressor of the NF-κB pathway and was recently shown to be frequently inactivated by deletions and/or point mutations in several types of B-cell lymphomas. Here, we studied 48 CLL, including at least 12 cases with a deletion of one allele of TNFAIP3, for mutations. However, only one case harboured a silent mutation, all other cases were unmutated. Therefore, A20 inactivation plays no significant role in the pathogenesis of CLL, and the recurrent deletion in CLL on 6q21-23, where TNFAIP3 is located, likely affects other gene(s).
Philipp
Claudia
C
Institute of Cell Biology, University of Duisburg-Essen, Medical School, Essen, Germany.
Edelmann
Jennifer
J
Bühler
Andreas
A
Winkler
Dirk
D
Stilgenbauer
Stephan
S
Küppers
Ralf
R
D000368:Aged; D002896:Chromosomes, Human, Pair 6; D004252:DNA Mutational Analysis / Q000379:methods*; D004268:DNA-Binding Proteins; D005091:Exons; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3