TY - JOUR
T1 - Timing the initiation of multiple myeloma.
T2 - Nature Communications
AU - Rustad, Even H.
AU - Yellapantula, Venkata
AU - Leongamornlert, Daniel
AU - Bolli, Niccolò
AU - Ledergor, Guy
AU - Nadeu, Ferran
AU - Angelopoulos, Nicos
AU - Dawson, Kevin J.
AU - Mitchell, Thomas J.
AU - Osborne, Robert J.
AU - Ziccheddu, Bachisio
AU - Carniti, Cristiana
AU - Montefusco, Vittorio
AU - Corradini, Paolo
AU - Anderson, Kenneth C.
AU - Moreau, Philippe
AU - Papaemmanuil, Elli
AU - Alexandrov, Ludmil B.
AU - Puente, Xose S.
AU - Campo, Elias
AU - Siebert, Reiner
AU - Avet-Loiseau, Herve
AU - Landgren, Ola
AU - Munshi, Nikhil
AU - Campbell, Peter J.
AU - Maura, Francesco
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-020-15740-9
DO - 10.1038/s41467-020-15740-9
M3 - Article
VL - 11
JO - Nat. Commun.
JF - Nat. Commun.
SN - 2041-1723
ER -