Mutational analysis of the IκBα gene in activated B cell-like diffuse large B-cell lymphoma

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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 κB (NFκB). We sought to determine whether mutations in the IκBα gene – the predominant inhibitor of NFκB – might play a role in the pathogenesis of ABC-DLBCL. All exons of the IκBα 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 IκBα gene. We conclude that mutations in the IκBα gene do not play a dominant role in the pathogenesis of ABC-DLBCL.

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