Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution
File(s)
Author(s)
Type
Journal Article
Abstract
The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.
Date Issued
2017-05-25
Date Acceptance
2017-04-13
Citation
NATURE, 2017, 545, pp.446-451
ISSN
0028-0836
Publisher
NATURE PUBLISHING GROUP
Start Page
446
End Page
451
Journal / Book Title
NATURE
Volume
545
Copyright Statement
© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. The final publication is available at https://dx.doi.org/10.1038/nature22364
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000401906500045&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CIRCULATING TUMOR DNA
NEGATIVE BREAST-CANCER
UPTAKE RATIO
FDG PET
STATISTICS
MUTATIONS
CARCINOMA
IMPACT
Publication Status
Published
Date Publish Online
2017-04-26