The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma

dc.contributor.authorBoyle, Eileen M.
dc.contributor.authorDeshpande, Shayu
dc.contributor.authorTytarenko, Ruslana
dc.contributor.authorAshby, Cody
dc.contributor.authorWang, Yan
dc.contributor.authorBauer, Michael A.
dc.contributor.authorJohnson, Sarah K.
dc.contributor.authorWardell, Christopher P.
dc.contributor.authorThanendrarajan, Sharmilan
dc.contributor.authorZangari, Maurizio
dc.contributor.authorFacon, Thierry
dc.contributor.authorDumontet, Charles
dc.contributor.authorBarlogie, Bart
dc.contributor.authorArbini, Arnaldo
dc.contributor.authorRustad, Even H.
dc.contributor.authorMaura, Francesco
dc.contributor.authorLandgren, Ola
dc.contributor.authorZhan, Fenghuang
dc.contributor.authorvan Rhee, Frits
dc.contributor.authorSchinke, Carolina
dc.contributor.authorDavies, Faith E.
dc.contributor.authorMorgan, Gareth J.
dc.contributor.authorWalker, Brian A.
dc.contributor.departmentMedicine, School of Medicine
dc.date.accessioned2024-03-18T10:02:07Z
dc.date.available2024-03-18T10:02:07Z
dc.date.issued2021-01-12
dc.description.abstractSmoldering myeloma (SMM) is associated with a high-risk of progression to myeloma (MM). We report the results of a study of 82 patients with both targeted sequencing that included a capture of the immunoglobulin and MYC regions. By comparing these results to newly diagnosed myeloma (MM) we show fewer NRAS and FAM46C mutations together with fewer adverse translocations, del(1p), del(14q), del(16q), and del(17p) in SMM consistent with their role as drivers of the transition to MM. KRAS mutations are associated with a shorter time to progression (HR 3.5 (1.5-8.1), p = 0.001). In an analysis of change in clonal structure over time we studied 53 samples from nine patients at multiple time points. Branching evolutionary patterns, novel mutations, biallelic hits in crucial tumour suppressor genes, and segmental copy number changes are key mechanisms underlying the transition to MM, which can precede progression and be used to guide early intervention strategies.
dc.eprint.versionFinal published version
dc.identifier.citationBoyle EM, Deshpande S, Tytarenko R, et al. The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma. Nat Commun. 2021;12(1):293. Published 2021 Jan 12. doi:10.1038/s41467-020-20524-2
dc.identifier.urihttps://hdl.handle.net/1805/39306
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/s41467-020-20524-2
dc.relation.journalNature Communications
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectMolecular medicine
dc.subjectCancer genomics
dc.subjectMutation
dc.titleThe molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma
dc.typeArticle
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