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- Title
Timing the initiation of multiple myeloma.
- Authors
Rustad, Even H.; Yellapantula, Venkata; Leongamornlert, Daniel; Bolli, Niccolò; Ledergor, Guy; Nadeu, 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, Elias
- 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. The initial mutational processes and how these lead to progression in multiple myeloma (MM) are unclear. Here, the authors identify mutational signatures that occur over time in a large cohort of MM patients and suggest features that may help in early diagnosis.
- Subjects
MULTIPLE myeloma; APOLIPOPROTEIN B; GERMINAL centers; EXOMES; EARLY diagnosis
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-15740-9