Neutral tumor evolution in myeloma is associated with poor prognosis.

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

Blood

journal_title

Blood

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

doi

10.1182/blood-2016-11-750612

subject

Has Abstract

pub_date

2017-10-05 00:00:00

pages

1639-1643

issue

14

eissn

0006-4971

issn

1528-0020

pii

blood-2016-11-750612

journal_volume

130

pub_type

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