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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). 1917-. ISSN 2041-1723

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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
Uncontrolled Keywords: Germinal Center; Humans; Multiple Myeloma; Cytidine Deaminase; Proteins; RNA, Messenger; Minor Histocompatibility Antigens; Linear Models; DNA Mutational Analysis; Genetics; Gene Expression Regulation, Neoplastic; RNA Editing; Mutation; Early Detection of Cancer; Single-Cell Analysis; Exome; APOBEC-1 Deaminase
Divisions: Faculty of Science and Health
Faculty of Science and Health > Computer Science and Electronic Engineering, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 08 Sep 2020 15:44
Last Modified: 18 Aug 2022 12:40

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