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2020-04-21

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cc-by (c) Rustad, Even H. et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/178864

Timing the initiation of multiple myeloma.

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https://doi.org/10.1038/s41467-020-15740-9

Resum

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.

Matèries

Mieloma múltiple, Etiologia

Matèries (anglès)

Multiple myeloma, Etiology

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Articles publicats en revistes (Fonaments Clínics)
<b>Publicacions de projectes de recerca finançats per la UE</b>

Citació

RUSTAD, Even h., YELLAPANTULA, Venkata, LEONGAMORNLERT, Daniel, BOLLI, Niccolò, LEDERGOR, Guy, NADEU PRAT, 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. Timing the initiation of multiple myeloma.. _Nature Communications_. 2020. Vol. 11, núm. 1917. [consulta: 22 de gener de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/178864]

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