| Literature DB >> 28827410 |
David C Johnson1, Oleg Lenive1, Jonathan Mitchell2, Graham Jackson3, Roger Owen4, Mark Drayson5, Gordon Cook6, John R Jones1, Charlotte Pawlyn1, Faith E Davies7, Brian A Walker7, Christopher Wardell7, Walter M Gregory8, David Cairns8, Gareth J Morgan7, Richard S Houlston1,2, Martin F Kaiser1.
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.Entities:
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Year: 2017 PMID： 28827410 PMCID： PMC5630010 DOI： 10.1182/blood-2016-11-750612
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113