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Blood Cancer J. 2019 Mar 26;9(4):39. doi: 10.1038/s41408-019-0199-3.

Deciphering the chronology of copy number alterations in Multiple Myeloma.

Author information

1
Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
2
Department of Biostatistics, Harvard T.H. Chan School of Public Health Boston, Boston, MA, 02115, USA.
3
Inserm UMR892, CNRS 6299, Université de Nantes; Centre Hospitalier Universitaire de Nantes, Unité Mixte de Genomique du Cancer, Nantes, France.
4
Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
5
VA Boston Healthcare System, Boston, MA, 02115, USA.
6
University Cancer Center of Toulouse Institut National de la Santé, Toulouse, France.
7
University Cancer Center of Toulouse Institut National de la Santé, Toulouse, France. avet-loiseau.h@chu-toulouse.fr.
8
Unité de Génomique du Myélome, IUC-Oncopole 2 Avenue Hubert Curien Cedex 1, Toulouse, 31037, France. avet-loiseau.h@chu-toulouse.fr.
9
Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA. nikhil_munshi@dfci.harvard.edu.
10
VA Boston Healthcare System, Boston, MA, 02115, USA. nikhil_munshi@dfci.harvard.edu.
11
Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA, 02215, USA. mehmet_samur@dfci.harvard.edu.
12
Department of Biostatistics, Harvard T.H. Chan School of Public Health Boston, Boston, MA, 02115, USA. mehmet_samur@dfci.harvard.edu.
13
Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA. mehmet_samur@dfci.harvard.edu.

Abstract

Multiple myeloma (MM) and its precursor condition MGUS are characterized by chromosomal aberrations. Here, we comprehensively characterize the order of occurrence of these complex genomic events underlying MM development using 500 MGUS, and MM samples. We identify hyperdiploid MM (HMM) and non-HMM as genomically distinct entities with different evolution of the copy number alterations. In HMM, gains of 9,15 or 19 are the first and clonal events observed as clonal even at MGUS stage. These events are thus early and may underlie initial transformation of normal plasma cells to MGUS cells. However, CNAs may not be adequate for progression to MM except in 15% of the patients in whom the complex subclonal deletion events are observed in MM but not MGUS. In NHMM, besides the driver translocations, clonal deletion of 13 and 1q gain are early events also observed in MGUS. We combined this information to propose a timeline for copy number alteration.

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