Genomic landscape and chronological reconstruction of driver events in multiple myeloma Journal Article
| Authors: | Maura, F.; Bolli, N.; Angelopoulos, N.; Dawson, K. J.; Leongamornlert, D.; Martincorena, I.; Mitchell, T. J.; Fullam, A.; Gonzalez, S.; Szalat, R.; Abascal, F.; Rodriguez-Martin, B.; Samur, M. K.; Glodzik, D.; Roncador, M.; Fulciniti, M.; Tai, Y. T.; Minvielle, S.; Magrangeas, F.; Moreau, P.; Corradini, P.; Anderson, K. C.; Tubio, J. M. C.; Wedge, D. C.; Gerstung, M.; Avet-Loiseau, H.; Munshi, N.; Campbell, P. J. |
| Article Title: | Genomic landscape and chronological reconstruction of driver events in multiple myeloma |
| Abstract: | 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. © 2019, The Author(s). |
| Journal Title: | Nature Communications |
| Volume: | 10 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2019-08-23 |
| Start Page: | 3835 |
| Language: | English |
| DOI: | 10.1038/s41467-019-11680-1 |
| PUBMED: | 31444325 |
| PROVIDER: | scopus |
| PMCID: | PMC6707220 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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