Neutral tumor evolution in myeloma is associated with poor prognosis.
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Embargo End Date
ICR Authors
Authors
Johnson, DC
Lenive, O
Mitchell, J
Jackson, G
Owen, R
Drayson, M
Cook, G
Jones, JR
Pawlyn, C
Davies, FE
Walker, BA
Wardell, C
Gregory, WM
Cairns, D
Morgan, GJ
Houlston, RS
Kaiser, MF
Lenive, O
Mitchell, J
Jackson, G
Owen, R
Drayson, M
Cook, G
Jones, JR
Pawlyn, C
Davies, FE
Walker, BA
Wardell, C
Gregory, WM
Cairns, D
Morgan, GJ
Houlston, RS
Kaiser, MF
Document Type
Journal Article
Date
2017-10-05
Date Accepted
2017-08-07
Abstract
Recent studies suggest that the evolutionary history of a cancer is important in forecasting clinical outlook. To gain insight into the clonal dynamics of multiple myeloma (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.
Citation
Blood, 2017, 130 (14), pp. 1639 - 1643
Source Title
Publisher
AMER SOC HEMATOLOGY
ISSN
0006-4971
eISSN
1528-0020
Research Team
Myeloma Biology and Therapeutics
Cancer Genomics
Myeloma Group
Cancer Genomics
Myeloma Group