Deciphering the chronology of copy number alterations in Multiple Myeloma

Anil Samur 1, 2 Stephane Minvielle 3 Masood Shammas 4, 5 Mariateresa Fulciniti 4 Florence Magrangeas 3 Paul Richardson 4 Philippe Moreau 3 Michel Attal 6 Kenneth Anderson 4 Giovanni Parmigiani 1, 2 Hervé Avet-Loiseau 6, 7, * Nikhil Munshi 4, 5, * Mehmet Samur 1, 2, *
* Corresponding author
1 Dana-Farber Cancer Institute [Boston]
2 Department of Biostatistics [Boston, MA, USA]
3 CRCNA - Centre de Recherche en Cancérologie / Nantes - Angers
4 Department of Medical Oncology [Boston, MA, USA]
5 VA Boston Healthcare System
6 Pôle IUC - Oncopole - Pôle Institut Universitaire du Cancer - Oncopole [CHU Toulouse]
7 Laboratoire de génomique du myélome [IUCT Oncopole, Toulouse]
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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Anil Samur, Stephane Minvielle, Masood Shammas, Mariateresa Fulciniti, Florence Magrangeas, et al.. Deciphering the chronology of copy number alterations in Multiple Myeloma. Blood Cancer Journal, Nature Publishing Group, 2019, 9 (4), pp.39. ⟨10.1038/s41408-019-0199-3⟩. ⟨inserm-02290251⟩

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