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Title: | Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities | Authors: | OBEN, Bénedith FROYEN, Guy Maclachlan, Kylee H. Leongamornlert, Daniel Abascal, Federico Zheng-Lin, Binbin Yellapantula, Venkata Derkach, Andriy GEERDENS, Ellen Diamond, Benjamin T. ARIJS, Ingrid MAES, Brigitte VANHEES, Kimberly Hultcrantz, Malin Manasanch, Elisabet E. Kazandjian, Dickran Lesokhin, Alexander Dogan, Ahmet Zhang, Yanming Mikulasova, Aneta Walker, Brian Morgan, Gareth Campbell, Peter J. Landgren, Ola RUMMENS, Jean-Luc Bolli, Niccolo Maura, Francesco |
Issue Date: | 2021 | Publisher: | NATURE RESEARCH | Source: | Nature Communications, 12 (1) (Art N° 1861) | 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. The factors that are associated with myeloma precursor condition progression are not well understood. Here the authors find that monoclonal gammopathies of undetermined significance and smoldering myelomas that did not progress to multiple myelomas have a distinct genomic profile and emerge later in the patient's life. | Notes: | Maura, F (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, 1275 York Ave, New York, NY 10021 USA.; Landgren, O; Maura, F (corresponding author), Univ Miami, Sylvester Comprehens Canc Ctr, Myeloma Program, Miami, FL 33124 USA. col15@miami.edu; fxm557@med.miami.edu |
Other: | Maura, F (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, 1275 York Ave, New York, NY 10021 USA. Landgren, O; Maura, F (corresponding author), Univ Miami, Sylvester Comprehens Canc Ctr, Myeloma Program, Miami, FL 33124 USA. col15@miami.edu; fxm557@med.miami.edu | Keywords: | DNA Copy Number Variations;Disease Progression;Genome, Human;Humans;Monoclonal Gammopathy of Undetermined Significance;Multiple Myeloma;Polymorphism, Single Nucleotide;Risk Factors;Smoldering Multiple Myeloma;Whole Genome Sequencing | Document URI: | http://hdl.handle.net/1942/34062 | e-ISSN: | 2041-1723 | DOI: | 10.1038/s41467-021-22140-0 | ISI #: | WOS:000637989400012 | Rights: | The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2022 |
Appears in Collections: | Research publications |
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