Neutral tumor evolution in myeloma is associated with poor prognosis.

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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

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

Notes