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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, Hervé 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) Publicacions de projectes de recerca finançats per la UE |
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