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Timing the initiation of multiple myeloma

Rustad, Even H and Yellapantula, Venkata and Leongamornlert, Daniel and Bolli, Niccolò and Ledergor, Guy and Nadeu, Ferran and Angelopoulos, Nicos and Dawson, Kevin J and Mitchell, Thomas J and Osborne, Robert J and Ziccheddu, Bachisio and Carniti, Cristiana and Montefusco, Vittorio and Corradini, Paolo and Anderson, Kenneth C and Moreau, Philippe and Papaemmanuil, Elli and Alexandrov, Ludmil B and Puente, Xose S and Campo, Elias and Siebert, Reiner and Avet-Loiseau, Herve and Landgren, Ola and Munshi, Nikhil and Campbell, Peter J and Maura, Francesco (2020) 'Timing the initiation of multiple myeloma.' Nature Communications, 11 (1). ISSN 2041-1723

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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 pre-malignant 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.

Item Type: Article
Divisions: Faculty of Science and Health > Computer Science and Electronic Engineering, School of
Depositing User: Elements
Date Deposited: 08 Sep 2020 15:44
Last Modified: 08 Sep 2020 16:15
URI: http://repository.essex.ac.uk/id/eprint/27601

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