TY - JOUR
T1 - The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma
AU - Boyle, Eileen M.
AU - Deshpande, Shayu
AU - Tytarenko, Ruslana
AU - Ashby, Cody
AU - Wang, Yan
AU - Bauer, Michael A.
AU - Johnson, Sarah K.
AU - Wardell, Christopher P.
AU - Thanendrarajan, Sharmilan
AU - Zangari, Maurizio
AU - Facon, Thierry
AU - Dumontet, Charles
AU - Barlogie, Bart
AU - Arbini, Arnaldo
AU - Rustad, Even H.
AU - Maura, Francesco
AU - Landgren, Ola
AU - Zhan, Fenghuang
AU - van Rhee, Frits
AU - Schinke, Carolina
AU - Davies, Faith E.
AU - Morgan, Gareth J.
AU - Walker, Brian A.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85099243690&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-20524-2
DO - 10.1038/s41467-020-20524-2
M3 - Article
C2 - 33436579
AN - SCOPUS:85099243690
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 293
ER -