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

Bénedith Oben; Guy Froyen; Kylee H. Maclachlan; Daniel Leongamornlert; Federico Abascal; Binbin Zheng-Lin; Venkata Yellapantula; Andriy Derkach; Ellen Geerdens; Benjamin T. Diamond; Ingrid Arijs; Brigitte Maes; Kimberly Vanhees; Malin Hultcrantz; Elisabet E. Manasanch; Dickran Kazandjian; Alexander Lesokhin; Ahmet Dogan; Yanming Zhang; Aneta Mikulasova; Brian Walker; Gareth Morgan; Peter J. Campbell; Ola Landgren; Jean Luc Rummens; Niccolò Bolli; Francesco Maura

doi:10.1038/s41467-021-22140-0

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

Bénedith Oben, Guy Froyen, Kylee H. Maclachlan, Daniel Leongamornlert, Federico Abascal, Binbin Zheng-Lin, Venkata Yellapantula, Andriy Derkach, Ellen Geerdens, Benjamin T. Diamond, Ingrid Arijs, Brigitte Maes, Kimberly Vanhees, Malin Hultcrantz, Elisabet E. Manasanch, Dickran Kazandjian, Alexander Lesokhin, Ahmet Dogan, Yanming Zhang, Aneta MikulasovaBrian Walker, Gareth Morgan, Peter J. Campbell, Ola Landgren, Jean Luc Rummens, Niccolò Bolli, Francesco Maura

Lymphoma-Myeloma

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

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.

Original language	English (US)
Article number	1861
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-22140-0
State	Published - Dec 1 2021

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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., ... Maura, F. (2021). Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities. Nature communications, 12(1), Article 1861. https://doi.org/10.1038/s41467-021-22140-0

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, JL, Bolli, N & Maura, F 2021, 'Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities', Nature communications, vol. 12, no. 1, 1861. https://doi.org/10.1038/s41467-021-22140-0

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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{\textquoteright}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.",

author = "B{\'e}nedith Oben and Guy Froyen and Maclachlan, {Kylee H.} and Daniel Leongamornlert and Federico Abascal and Binbin Zheng-Lin and Venkata Yellapantula and Andriy Derkach and Ellen Geerdens and Diamond, {Benjamin T.} and Ingrid Arijs and Brigitte Maes and Kimberly Vanhees and Malin Hultcrantz and Manasanch, {Elisabet E.} and Dickran Kazandjian and Alexander Lesokhin and Ahmet Dogan and Yanming Zhang and Aneta Mikulasova and Brian Walker and Gareth Morgan and Campbell, {Peter J.} and Ola Landgren and Rummens, {Jean Luc} and Niccol{\`o} Bolli and Francesco Maura",

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AU - Oben, Bénedith

AU - Froyen, Guy

AU - Maclachlan, Kylee H.

AU - Leongamornlert, Daniel

AU - Abascal, Federico

AU - Zheng-Lin, Binbin

AU - Yellapantula, Venkata

AU - Derkach, Andriy

AU - Geerdens, Ellen

AU - Diamond, Benjamin T.

AU - Arijs, Ingrid

AU - Maes, Brigitte

AU - Vanhees, Kimberly

AU - Hultcrantz, Malin

AU - Manasanch, Elisabet E.

AU - Kazandjian, Dickran

AU - Lesokhin, Alexander

AU - Dogan, Ahmet

AU - Zhang, Yanming

AU - Mikulasova, Aneta

AU - Walker, Brian

AU - Morgan, Gareth

AU - Campbell, Peter J.

AU - Landgren, Ola

AU - Rummens, Jean Luc

AU - Bolli, Niccolò

AU - Maura, Francesco

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

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

Abstract

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