title: Mutational analysis of the IkappaBalpha gene in activated B cell-like diffuse large B-cell lymphoma.
abstract: The lymphoma cells of the activated B cell-like (ABC-) subtype of diffuse large B-cell lymphoma (DLBCL) show constitutive activity of the transcription factor, nuclear factor kappaB (NFkappaB). We sought to determine whether mutations in the IkappaBalpha gene - the predominant inhibitor of NFkappaB - might play a role in the pathogenesis of ABC-DLBCL. All exons of the IkappaBalpha gene were directly sequenced from 10 cases of immunohistochemically classified ABC-DLBCL and from six non-ABC-DLBCL cases. Two novel polymorphisms were identified, based on their presence in tumour as well as non-tumour DNA of the respective patients: a duplication near the transcriptional start and a single nucleotide exchange in exon 1. A somatic missense mutation was identified in exon 3, in addition to a wild-type sequence in only one ABC-DLBCL case. Thus, also in this case no clonal biallelic inactivating mutation was present in the IkappaBalpha gene. We conclude that mutations in the IkappaBalpha gene do not play a dominant role in the pathogenesis of ABC-DLBCL.
authors.affiliation: Molecular Tumor Biology and Tumor Immunology, University of Cologne, Cologne, Germany.
authors.forename: Roman K
authors.initials: RK
authors.lastname: Thomas
authors.forename: Claudia
authors.initials: C
authors.lastname: Wickenhauser
authors.forename: Samir
authors.initials: S
authors.lastname: Tawadros
authors.forename: Volker
authors.initials: V
authors.lastname: Diehl
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
authors.forename: Roland
authors.initials: R
authors.lastname: Schmitz
mesh_terms: D004252:DNA Mutational Analysis; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D016130:Immunophenotyping / Q000379:methods; D016393:Lymphoma, B-Cell / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D000072000:NF-KappaB Inhibitor alpha; D011110:Polymorphism, Genetic
chemical_list: D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha