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.
journal_name
Bloodjournal_title
Bloodauthors
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 MFdoi
10.1182/blood-2016-11-750612subject
Has Abstractpub_date
2017-10-05 00:00:00pages
1639-1643issue
14eissn
0006-4971issn
1528-0020pii
blood-2016-11-750612journal_volume
130pub_type
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