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|Title:||Timing the initiation of multiple myeloma.|
|Author:||Rustad, Even H.|
Dawson, Kevin J.
Mitchell, Thomas J.
Osborne, Robert J.
Anderson, Kenneth C.
Alexandrov, Ludmil B.
Puente, Xose S.
Campo Güerri, Elias
Avet Loiseau, Herve
Campbell, Peter J.
|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|
|Appears in Collections:||Articles publicats en revistes (Fonaments Clínics)|
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