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 |