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dc.contributor.authorPettersen, Henrik Sahlin
dc.contributor.authorGalashevskaya, Anastasia
dc.contributor.authorDoseth, Berit
dc.contributor.authorSousa, Mirta
dc.contributor.authorSarno, Antonio
dc.contributor.authorVisnes, Torkild
dc.contributor.authorAas, Per Arne
dc.contributor.authorLiabakk, Nina-Beate
dc.contributor.authorSlupphaug, Geir
dc.contributor.authorSætrom, Pål
dc.contributor.authorKavli, Bodil Merete
dc.contributor.authorKrokan, Hans Einar
dc.identifier.citationDNA Repair 2014, 25:60-71nb_NO
dc.description.abstracttThe most common mutations in cancer are C to T transitions, but their origin has remained elusive.Recently, mutational signatures of APOBEC-family cytosine deaminases were identified in many com-mon cancers, suggesting off-target deamination of cytosine to uracil as a common mutagenic mechanism.Here we present evidence from mass spectrometric quantitation of deoxyuridine in DNA that shows sig-nificantly higher genomic uracil content in B-cell lymphoma cell lines compared to non-lymphoma cancercell lines and normal circulating lymphocytes. The genomic uracil levels were highly correlated with AIDmRNA and protein expression, but not with expression of other APOBECs. Accordingly, AID knockdownsignificantly reduced genomic uracil content. B-cells stimulated to express endogenous AID and undergoclass switch recombination displayed a several-fold increase in total genomic uracil, indicating that Bcells may undergo widespread cytosine deamination after stimulation. In line with this, we found thatclustered mutations (kataegis) in lymphoma and chronic lymphocytic leukemia predominantly carryAID-hotspot mutational signatures. Moreover, we observed an inverse correlation of genomic uracil withuracil excision activity and expression of the uracil-DNA glycosylases UNG and SMUG1. In conclusion,AID-induced mutagenic U:G mismatches in DNA may be a fundamental and common cause of mutationsin B-cell malignancies.nb_NO
dc.rightsNavngivelse 3.0 Norge*
dc.titleAID expression in B-cell lymphomas causes accumulation of genomic uracil and a distinct AID mutational signaturenb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalDNA Repairnb_NO
dc.description.localcode© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-NDlicense (

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Navngivelse 3.0 Norge
Except where otherwise noted, this item's license is described as Navngivelse 3.0 Norge