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Article Dans Une Revue Nature Communications Année : 2019

Genomic landscape and chronological reconstruction of driver events in multiple myeloma

David C Wedge
  • Fonction : Auteur

Résumé

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.

Domaines

Cancer
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Dates et versions

inserm-02290176 , version 1 (17-09-2019)

Identifiants

Citer

Francesco Maura, Niccolo Bolli, Nicos Angelopoulos, Kevin J Dawson, Daniel Leongamornlert, et al.. Genomic landscape and chronological reconstruction of driver events in multiple myeloma. Nature Communications, 2019, 10 (1), pp.3835. ⟨10.1038/s41467-019-11680-1⟩. ⟨inserm-02290176⟩
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