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


Authors: Oben, B.; Froyen, G.; Maclachlan, K. H.; Leongamornlert, D.; Abascal, F.; Zheng-Lin, B.; Yellapantula, V.; Derkach, A.; Geerdens, E.; Diamond, B. T.; Arijs, I.; Maes, B.; Vanhees, K.; Hultcrantz, M.; Manasanch, E. E.; Kazandjian, D.; Lesokhin, A.; Dogan, A.; Zhang, Y.; Mikulasova, A.; Walker, B.; Morgan, G.; Campbell, P. J.; Landgren, O.; Rummens, J. L.; Bolli, N.; Maura, F.
Article Title: Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities
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. © 2021, The Author(s).
Keywords: single nucleotide polymorphism; genetics; mutation; polymorphism, single nucleotide; genetic analysis; multiple myeloma; gene expression; biology; risk factors; pathology; risk factor; disease progression; human genome; genomics; genome; tumor; monoclonal immunoglobulinemia; disease exacerbation; antibody; genome, human; dna copy number variations; copy number variation; smoldering multiple myeloma; cancer; humans; human; whole genome sequencing; monoclonal gammopathy of undetermined significance
Journal Title: Nature Communications
Volume: 12
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2021-03-25
Start Page: 1861
Language: English
DOI: 10.1038/s41467-021-22140-0
PUBMED: 33767199
PROVIDER: scopus
PMCID: PMC7994386
DOI/URL:
Notes: Article -- Export Date: 3 May 2021 -- Source: Scopus
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MSK Authors
  1. Alexander Meyer Lesokhin
    153 Lesokhin
  2. Ahmet Dogan
    280 Dogan
  3. Yanming Zhang
    98 Zhang
  4. Francesco Maura
    35 Maura
  5. Benjamin Diamond
    13 Diamond
  6. Andriy Derkach
    10 Derkach
  7. Binbin Zheng
    2 Zheng