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Type: Journal article
Title: Subclonal evolution in disease progression from MGUS/SMM to multiple myeloma is characterised by clonal stability
Author: Dutta, A.
Fink, J.
Grady, J.
Morgan, G.
Mullighan, C.
To, L.
Hewett, D.
Zannettino, A.
Citation: Leukemia, 2019; 33(2):457-468
Publisher: Nature
Issue Date: 2019
ISSN: 0887-6924
Statement of
Ankit K. Dutta, J. Lynn Fink, John P. Grady, Gareth J. Morgan, Charles G. Mullighan, Luen B. To, Duncan R. Hewett, Andrew C. W. Zannettino
Abstract: Multiple myeloma (MM) is a largely incurable haematological malignancy defined by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow. Clonal heterogeneity has recently been established as a feature in MM, however, the subclonal evolution associated with disease progression has not been described. Here, we performed whole-exome sequencing of serial samples from 10 patients, providing new insights into the progression from monoclonal gammopathy of undetermined significance (MGUS) and smouldering MM (SMM), to symptomatic MM. We confirm that intraclonal genetic heterogeneity is a common feature at diagnosis and that the driving events involved in disease progression are more subtle than previously reported. We reveal that MM evolution is mainly characterised by the phenomenon of clonal stability, where the transformed subclonal PC populations identified at MM are already present in the asymptomatic MGUS/SMM stages. Our findings highlight the possibility that PC extrinsic factors may play a role in subclonal evolution and MGUS/SMM to MM progression.
Keywords: Cells, Cultured; Humans; Multiple Myeloma; Disease Progression; Prognosis; Cohort Studies; Longitudinal Studies; Follow-Up Studies; Monoclonal Gammopathy of Undetermined Significance; Clonal Evolution; Biomarkers, Tumor; Whole Exome Sequencing
Rights: © The Author(s) 2018. This article is published with open access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.
RMID: 0030095405
DOI: 10.1038/s41375-018-0206-x
Grant ID:
Appears in Collections:Medicine publications

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