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

Eileen M. Boyle, Shayu Deshpande, Ruslana Tytarenko, Cody Ashby, Yan Wang, Michael A. Bauer, Sarah K. Johnson, Christopher P. Wardell, Sharmilan Thanendrarajan, Maurizio Zangari, Thierry Facon, Charles Dumontet, Bart Barlogie, Arnaldo Arbini, Even H. Rustad, Francesco Maura, Ola Landgren, Fenghuang Zhan, Frits van Rhee, Carolina SchinkeFaith E. Davies, Gareth J. Morgan, Brian A. Walker

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Smoldering 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.

Original languageEnglish (US)
Article number293
JournalNature communications
Issue number1
StatePublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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