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dc.contributor.authorRustad, Even H.-
dc.contributor.authorYellapantula, Venkata-
dc.contributor.authorLeongamornlert, Daniel-
dc.contributor.authorBolli, Niccolò-
dc.contributor.authorLedergor, Guy-
dc.contributor.authorNadeu, Ferran-
dc.contributor.authorAngelopoulos, Nicos-
dc.contributor.authorDawson, Kevin J.-
dc.contributor.authorMitchell, Thomas J.-
dc.contributor.authorOsborne, Robert J.-
dc.contributor.authorZiccheddu, Bachisio-
dc.contributor.authorCarniti, Cristiana-
dc.contributor.authorMontefusco, Vittorio-
dc.contributor.authorCorradini, Paolo-
dc.contributor.authorAnderson, Kenneth C.-
dc.contributor.authorMoreau, Philippe-
dc.contributor.authorPapaemmanuil, Elli-
dc.contributor.authorAlexandrov, Ludmil B.-
dc.contributor.authorPuente, Xose S.-
dc.contributor.authorCampo Güerri, Elias-
dc.contributor.authorSiebert, Reiner-
dc.contributor.authorAvet Loiseau, Herve-
dc.contributor.authorLandgren, Ola-
dc.contributor.authorMunshi, Nikhil-
dc.contributor.authorCampbell, Peter J.-
dc.contributor.authorMaura, Francesco-
dc.description.abstractThe evolution and progression of multiple myeloma and its precursors over time is poorly understood. Here, we investigate the landscape and timing of mutational processes shaping multiple myeloma evolution in a large cohort of 89 whole genomes and 973 exomes. We identify eight processes, including a mutational signature caused by exposure to melphalan. Reconstructing the chronological activity of each mutational signature, we estimate that the initial transformation of a germinal center B-cell usually occurred during the first 2nd-3rd decades of life. We define four main patterns of activation-induced deaminase (AID) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutagenesis over time, including a subset of patients with evidence of prolonged AID activity during the premalignant phase, indicating antigen-responsiveness and germinal center reentry. Our findings provide a framework to study the etiology of multiple myeloma and explore strategies for prevention and early detection.-
dc.format.extent14 p.-
dc.publisherNature Publishing Group-
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofNature Communications, 2020, vol. 11, num. 1917-
dc.rightscc-by (c) Rustad, Even H. et al., 2020-
dc.subject.classificationMieloma múltiple-
dc.subject.otherMultiple myeloma-
dc.titleTiming the initiation of multiple myeloma.-
Appears in Collections:Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (Fonaments Clínics)

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