RT Journal Article
T1 Genomic landscape and chronological reconstruction of driver events in multiple myeloma
A1 Maura, Francesco
A1 Bolli, Niccoló
A1 Angelopoulos, Nicos
A1 Dawson, Kevin J.
A1 Leongamornlert, Daniel
A1 Martincorena, Inigo
A1 Mitchell, Thomas J.
A1 Fullam, Anthony
A1 González Rosado, Santiago
A1 Szalat, Raphael
A1 Abascal, Federico
A1 Rodríguez Martín, Bernardo
A1 Kemal Samur, Mehmet
A1 Glodzik, Dominik
A1 Roncador, Marco
A1 Fulciniti, Mariateresa
A1 Tai, Yu Tzu
A1 Minvielle, Stephane
A1 Magrangeas, Florence
A1 Moreau, Philippe
A1 Corradini, Paolo
A1 Anderson, Kenneth C.
A1 Castro Tubío, José Manuel
A1 Wedge, David C.
A1 Gerstung, Moritz
A1 Avet-Loiseau, Hervé
A1 Munshi, Nikhil
A1 Campbell, Peter J.
K1 Cancer genomics
K1 Myeloma
AB The multiple myeloma (MM) genome is heterogeneous and evolves through preclinical and post-diagnosis phases. Here we report a catalog and hierarchy of driver lesions using sequences from 67 MM genomes serially collected from 30 patients together with public exome datasets. Bayesian clustering defines at least 7 genomic subgroups with distinct sets of co-operating events. Focusing on whole genome sequencing data, complex structural events emerge as major drivers, including chromothripsis and a novel replication-based mechanism of templated insertions, which typically occur early. Hyperdiploidy also occurs early, with individual trisomies often acquired in different chronological windows during evolution, and with a preferred order of acquisition. Conversely, positively selected point mutations, whole genome duplication and chromoplexy events occur in later disease phases. Thus, initiating driver events, drawn from a limited repertoire of structural and numerical chromosomal changes, shape preferred trajectories of evolution that are biologically relevant but heterogeneous across patients.
PB Nature Publishing Group
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21835
UL http://hdl.handle.net/10347/21835
LA eng
NO Maura, F., Bolli, N., Angelopoulos, N. et al. Genomic landscape and chronological reconstruction of driver events in multiple myeloma. Nat Commun 10, 3835 (2019). https://doi.org/10.1038/s41467-019-11680-1
NO F.M. is supported by AIL (Associazione Italiana Contro le Leucemie-Linfomi e Mieloma ONLUS), by SIES (Società Italiana di Ematologia Sperimentale), and by the Memorial Sloan Kettering Cancer Center NCI Core Grant (P30 CA 008748). N.B. is funded by AIRC (Associazione Italiana per la Ricerca sul Cancro) through a MFAG (no. 17658) and by the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 817997). This work was supported by Department of Veterans Affairs Merit Review Award I01BX001584-01 (N.C.M.), NIH grants P01-155258 (N.C.M., H.A.L., M.F., P.J.C. and K.C.A.) and 5P50CA100707-13 (N.C.M., H.A.L. and K.C.A)
DS Minerva
RD 23 abr 2026