Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities

Bénedith Oben, Guy Froyen, Kylee H. Maclachlan, Daniel Leongamornlert, Federico Abascal, Binbin Zheng-Lin, Venkata Yellapantula, Andriy Derkach, Ellen Geerdens, Benjamin T. Diamond, Ingrid Arijs, Brigitte Maes, Kimberly Vanhees, Malin Hultcrantz, Elisabet E. Manasanch, Dickran Kazandjian, Alexander Lesokhin, Ahmet Dogan, Yanming Zhang, Aneta Mikulasova, Brian Walker, Gareth Morgan, Peter J. Campbell, Ola Landgren (), Jean-Luc Rummens, Niccolò Bolli and Francesco Maura ()
Additional contact information
Bénedith Oben: Jessa Hospital
Guy Froyen: Hasselt University
Kylee H. Maclachlan: Memorial Sloan Kettering Cancer Center
Daniel Leongamornlert: Wellcome Sanger Institute
Federico Abascal: Wellcome Sanger Institute
Binbin Zheng-Lin: Memorial Sloan Kettering Cancer Center
Venkata Yellapantula: Memorial Sloan Kettering Cancer Center
Andriy Derkach: Memorial Sloan Kettering Cancer Center
Ellen Geerdens: Jessa Hospital
Benjamin T. Diamond: Memorial Sloan Kettering Cancer Center
Ingrid Arijs: Hasselt University
Brigitte Maes: Jessa Hospital
Kimberly Vanhees: Hasselt University
Malin Hultcrantz: Memorial Sloan Kettering Cancer Center
Elisabet E. Manasanch: The University of Texas MD Anderson Cancer Center
Dickran Kazandjian: National Institutes of Health
Alexander Lesokhin: Memorial Sloan Kettering Cancer Center
Ahmet Dogan: Memorial Sloan Kettering Cancer Center
Yanming Zhang: Memorial Sloan Kettering Cancer Center
Aneta Mikulasova: Newcastle University
Brian Walker: Indiana University
Gareth Morgan: New York University Langone Health
Peter J. Campbell: Wellcome Sanger Institute
Ola Landgren: University of Miami
Jean-Luc Rummens: Jessa Hospital
Niccolò Bolli: University of Milan
Francesco Maura: Memorial Sloan Kettering Cancer Center

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Multiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n = 15) are characterized by later initiation in the patient’s life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable.

Date: 2021
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DOI: 10.1038/s41467-021-22140-0

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