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

Lookup NU author(s): Dr Daniel Leongamornlert, Dr Aneta Mikulasova

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021, The Author(s).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.


Publication metadata

Author(s): Oben B, Froyen G, Maclachlan KH, Leongamornlert D, Abascal F, Zheng-Lin B, Yellapantula V, Derkach A, Geerdens E, Diamond BT, Arijs I, Maes B, Vanhees K, Hultcrantz M, Manasanch EE, Kazandjian D, Lesokhin A, Dogan A, Zhang Y, Mikulasova A, Walker B, Morgan G, Campbell PJ, Landgren O, Rummens J-L, Bolli N, Maura F

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2021

Volume: 12

Issue: 1

Online publication date: 25/03/2021

Acceptance date: 23/02/2021

Date deposited: 14/04/2021

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41467-021-22140-0

DOI: 10.1038/s41467-021-22140-0

PubMed id: 33767199


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Funding

Funder referenceFunder name
817997
ERC
P30 CA 008748
P30 CA 240139

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