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

被引：80

作者：

Boyle, Eileen M. ^{[1
,2
,3
]}

Deshpande, Shayu ^{[1
]}

Tytarenko, Ruslana ^{[1
]}

Ashby, Cody ^{[1
,4
]}

Wang, Yan ^{[1
]}

Bauer, Michael A. ^{[1
,4
]}

Johnson, Sarah K. ^{[1
]}

Wardell, Christopher P. ^{[1
,4
]}

Thanendrarajan, Sharmilan ^{[1
]}

Zangari, Maurizio ^{[1
]}

Facon, Thierry ^{[5
]}

Dumontet, Charles ^{[2
]}

Barlogie, Bart ^{[6
]}

Arbini, Arnaldo ^{[3
]}

Rustad, Even H. ^{[3
]}

Maura, Francesco ^{[7
]}

Landgren, Ola ^{[7
]}

Zhan, Fenghuang ^{[1
]}

van Rhee, Frits ^{[1
]}

Schinke, Carolina ^{[1
]}

Davies, Faith E. ^{[3
]}

Morgan, Gareth J. ^{[3
]}

Walker, Brian A. ^{[8
]}

机构：

[1] Univ Arkansas Med Sci, Myeloma Ctr, Little Rock, AR 72205 USA

[2] Canc Res Ctr Lyon, INSERM 1052, CNRS 5286, Lyon, France

[3] NYU Langone Hlth, Perlmutter Canc Ctr, New York, NY 10016 USA

[4] Univ Arkansas Med Sci, Dept Biomed Informat, Little Rock, AR 72205 USA

[5] Lille Univ Hosp, Serv Malad Sang, Hop Claude Huriez, Lille, France

[6] Mt Sinai Hosp, Div Hematol, New York, NY 10029 USA

[7] Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, 1275 York Ave, New York, NY 10021 USA

[8] Indiana Univ, Div Hematol Oncol, Indianapolis, IN 46204 USA

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

COPY NUMBER; PROGRESSION; RISK; LESIONS; ABNORMALITIES; PREDICT; MODEL;

D O I：

10.1038/s41467-020-20524-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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