The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2021

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

Eileen Boyle
  • Fonction : Auteur
Shayu Deshpande
  • Fonction : Auteur
Ruslana Tytarenko
  • Fonction : Auteur
Cody Ashby
Yan Wang
  • Fonction : Auteur
Michael Bauer
Sarah Johnson
  • Fonction : Auteur
Christopher Wardell
Sharmilan Thanendrarajan
  • Fonction : Auteur
Maurizio Zangari
  • Fonction : Auteur
Thierry Facon
  • Fonction : Auteur
Bart Barlogie
  • Fonction : Auteur
Arnaldo Arbini
  • Fonction : Auteur
Even Rustad
  • Fonction : Auteur
Francesco Maura
Ola Landgren
Fenghuang Zhan
  • Fonction : Auteur
Frits van Rhee
  • Fonction : Auteur
Carolina Schinke
Faith Davies
  • Fonction : Auteur
Gareth Morgan
Brian Walker

Résumé

Abstract 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.

Dates et versions

hal-03810061 , version 1 (11-10-2022)

Identifiants

Citer

Eileen Boyle, Shayu Deshpande, Ruslana Tytarenko, Cody Ashby, Yan Wang, et al.. The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma. Nature Communications, 2021, 12 (1), pp.293. ⟨10.1038/s41467-020-20524-2⟩. ⟨hal-03810061⟩
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