Neutral tumor evolution in myeloma is associated with poor prognosis

被引：1

作者：

Johnson, David C. ^{[1
]}

Lenive, Oleg ^{[1
]}

Mitchell, Jonathan ^{[2
]}

Jackson, Graham ^{[3
]}

Owen, Roger ^{[4
]}

Drayson, Mark ^{[5
]}

Cook, Gordon ^{[6
]}

Jones, John R. ^{[1
]}

Pawlyn, Charlotte ^{[1
]}

Davies, Faith E. ^{[7
]}

Walker, Brian A. ^{[7
]}

Wardell, Christopher ^{[7
]}

Gregory, Walter M. ^{[8
]}

Cairns, David ^{[8
]}

Morgan, Gareth J. ^{[7
]}

Houlston, Richard S. ^{[1
,2
]}

Kaiser, Martin F. ^{[1
]}

机构：

[1] Inst Canc Res, Div Mol Pathol, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England

[2] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England

[3] Newcastle Univ, Dept Haematol, Newcastle, England

[4] St James Univ Hosp, Leeds, W Yorkshire, England

[5] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England

[6] St James Univ Hosp, Dept Haematol, Leeds, W Yorkshire, England

[7] Univ Arkansas Med Sci, Myeloma Inst, Little Rock, AR 72205 USA

[8] Univ Leeds, Leeds Inst Clin Trials Res, Clin Trial Res Unit, Leeds, W Yorkshire, England

来源：

BLOOD | 2017年 / 130卷 / 14期

基金：

美国国家卫生研究院;

关键词：

MULTIPLE-MYELOMA; CANCER EVOLUTION; SPECTRUM; GROWTH;

D O I：

10.1182/blood-2016-11750612

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recent studies suggest that the evolutionary history of a cancer is important in forecasting clinical outlook. To gain insight into the clonal dynamics ofmultiplemyeloma (MM) and its possible influence on patient outcomes, we analyzed whole exome sequencing tumor data for 333 patients from Myeloma XI, a UK phase 3 trial and 434 patients from the CoMMpass study, all of which had received immunomodulatory drug (IMiD) therapy. By analyzing mutant allele frequency distributions in tumors, we found that 17% to 20% of MM is under neutral evolutionary dynamics. These tumors are associated with poorer patient survival in nonintensively treated patients, which is consistent with the reduced therapeutic efficacy of microenvironment- modulating IMiDs. Our findings provide evidence that knowledge of the evolutionary history of MM has relevance for predicting patient outcomes and personalizing therapy.

引用

页码：1639 / 1643

页数：5

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