Genomic landscape and chronological reconstruction of driver events in multiple myeloma

Francesco Maura, Niccoló Bolli, Nicos Angelopoulos, Kevin J. Dawson, Daniel Leongamornlert, Inigo Martincorena, Thomas J. Mitchell, Anthony Fullam, Santiago Gonzalez, Raphael Szalat, Federico Abascal, Bernardo Rodriguez-Martin, Mehmet Kemal Samur, Dominik Glodzik, Marco Roncador, Mariateresa Fulciniti, Yu Tzu Tai, Stephane Minvielle, Florence Magrangeas, Philippe Moreau, Paolo Corradini, Kenneth C. Anderson, Jose M. C. Tubio, David C. Wedge, Moritz Gerstung, Hervé Avet-Loiseau, Nikhil Munshi () and Peter J. Campbell ()
Additional contact information
Francesco Maura: Memorial Sloan Kettering Cancer Center
Niccoló Bolli: University of Milan
Nicos Angelopoulos: Wellcome Sanger Institute
Kevin J. Dawson: Wellcome Sanger Institute
Daniel Leongamornlert: Wellcome Sanger Institute
Inigo Martincorena: Wellcome Sanger Institute
Thomas J. Mitchell: Wellcome Sanger Institute
Anthony Fullam: Wellcome Sanger Institute
Santiago Gonzalez: European Molecular Biology Laboratory (EMBL-EBI)
Raphael Szalat: Harvard Medical School
Federico Abascal: Wellcome Sanger Institute
Bernardo Rodriguez-Martin: University of Santiago de Compostela
Mehmet Kemal Samur: Harvard Medical School
Dominik Glodzik: Wellcome Sanger Institute
Marco Roncador: Wellcome Sanger Institute
Mariateresa Fulciniti: Harvard Medical School
Yu Tzu Tai: Harvard Medical School
Stephane Minvielle: Université d’Angers, Université de Nantes
Florence Magrangeas: Université d’Angers, Université de Nantes
Philippe Moreau: Université d’Angers, Université de Nantes
Paolo Corradini: University of Milan
Kenneth C. Anderson: Harvard Medical School
Jose M. C. Tubio: Wellcome Sanger Institute
David C. Wedge: University of Oxford, Big Data Institute
Moritz Gerstung: European Molecular Biology Laboratory (EMBL-EBI)
Hervé Avet-Loiseau: IUC-Oncopole, and CRCT INSERM U1037
Nikhil Munshi: Harvard Medical School
Peter J. Campbell: Wellcome Sanger Institute

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11680-1

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DOI: 10.1038/s41467-019-11680-1

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