期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22140-0
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资金
- Society of Memorial Sloan Kettering
- Sylvester Comprehensive Cancer Center NCI Core Grant [P30 CA 240139]
- Memorial Sloan Kettering Cancer Center NCI Core Grant [P30 CA 008748]
- Multiple Myeloma Research Foundation (MMRF)
- Perelman Family Foundation
- Riney Family Multiple Myeloma Research Program Fund
- American Society of Hematology
- International Myeloma Foundation
- Society of Memorial Sloan Kettering Cancer Center
- Royal Australasian College of Physicians Dr. Helen Rarity McCreanor Traveling Fellowship
- foundation Limburg Sterk Merk (LSM)
- Hasselt University
- Ziekenhuis Oost-Limburg
- Jessa Hospital
- Limburgs Kankerfonds
- LiveALife
- European Research Council under the European Union's Horizon 2020 research and innovation program [817997]
The study demonstrates that MGUS and SMM that do not progress to multiple myeloma have a distinct genomic profile and emerge later in the patient's life.
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. The factors that are associated with myeloma precursor condition progression are not well understood. Here the authors find that monoclonal gammopathies of undetermined significance and smoldering myelomas that did not progress to multiple myelomas have a distinct genomic profile and emerge later in the patient's life.
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