Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/178864
Title: Timing the initiation of multiple myeloma.
Author: Rustad, Even H.
Yellapantula, Venkata
Leongamornlert, Daniel
Bolli, Niccolò
Ledergor, Guy
Nadeu, Ferran
Angelopoulos, Nicos
Dawson, Kevin J.
Mitchell, Thomas J.
Osborne, Robert J.
Ziccheddu, Bachisio
Carniti, Cristiana
Montefusco, Vittorio
Corradini, Paolo
Anderson, Kenneth C.
Moreau, Philippe
Papaemmanuil, Elli
Alexandrov, Ludmil B.
Puente, Xose S.
Campo Güerri, Elias
Siebert, Reiner
Avet Loiseau, Herve
Landgren, Ola
Munshi, Nikhil
Campbell, Peter J.
Maura, Francesco
Keywords: Mieloma múltiple
Etiologia
Multiple myeloma
Etiology
Issue Date: 21-Apr-2020
Publisher: Nature Publishing Group
Abstract: The 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.
Note: Reproducció del document publicat a: https://doi.org/10.1038/s41467-020-15740-9
It is part of: Nature Communications, 2020, vol. 11, num. 1917
URI: http://hdl.handle.net/2445/178864
Related resource: https://doi.org/10.1038/s41467-020-15740-9
ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)

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