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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/178864
Timing the initiation of multiple myeloma.
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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 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.
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RUSTAD, Even H., et al. Timing the initiation of multiple myeloma. Nature Communications. 2020. Vol. 11, num. 1917. ISSN 2041-1723. [consulted: 10 of June of 2026]. Available at: https://hdl.handle.net/2445/178864