Neutral tumor evolution in myeloma is associated with poor prognosis.
Date
2017-10-05Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Subject
Humans
Multiple Myeloma
Thalidomide
Immunosuppressive Agents
Immunologic Factors
Prognosis
Gene Frequency
Genetic Drift
Mutation
Female
Male
Kaplan-Meier Estimate
Tumor Microenvironment
Exome
Lenalidomide
Research team
Myeloma Biology and Therapeutics
Cancer Genomics
Myeloma Group
Language
eng
Date accepted
2017-08-07
License start date
2017-10
Citation
Blood, 2017, 130 (14), pp. 1639 - 1643
Publisher
AMER SOC HEMATOLOGY