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Title: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution
Authors: Abbosh, C.
Birkbak, N. J.
Wilson, G. A.
Jamal-Hanjani, M.
Constantin, T.
Salari, R.
Le Quesne, John
Moore, D. A.
Veeriah, S.
Rosenthal, R.
Marafioti, T.
Kirkizlar, E.
Watkins, T. B. K.
McGranahan, N.
Ward, S.
Martinson, L.
Riley, J.
Fraioli, F.
Al Bakir, M.
Grönroos, E.
Zambrana, F.
Endozo, R.
Bi, W. L.
Fennessy, F. M.
Sponer, N.
Johnson, D.
Laycock, J.
Shafi, S.
Czyzewska-Khan, J.
Rowan, A.
Chambers, T.
Matthews, N.
Turajlic, S.
Hiley, C.
Lee, S. M.
Forster, M. D.
Ahmad, T.
Falzon, M.
Borg, E.
Lawrence, D.
Hayward, M.
Kolvekar, S.
Panagiotopoulos, N.
Janes, S. M.
Thakrar, R.
Ahmed, A.
Blackhall, F.
Summers, Y.
Hafez, D.
Naik, A.
Ganguly, A.
Kareht, S.
Shah, R.
Joseph, L.
Marie Quinn, A.
Crosbie, P. A.
Naidu, B.
Middleton, G.
Langman, G.
Trotter, S.
Nicolson, M.
Remmen, H.
Kerr, K.
Chetty, M.
Gomersall, L.
Fennell, D. A.
Nakas, A.
Rathinam, S.
Anand, G.
Khan, S.
Russell, P.
Ezhil, V.
Ismail, B.
Irvin-Sellers, M.
Prakash, V.
Lester, J. F.
Kornaszewska, M.
Attanoos, R.
Adams, H.
Davies, H.
Oukrif, D.
Akarca, A. U.
Hartley, J. A.
Lowe, H. L.
Lock, S.
Iles, N.
Bell, H.
Ngai, Y.
Elgar, G.
Szallasi, Z.
Schwarz, R. F.
Herrero, J.
Stewart, A.
Quezada, S. A.
Peggs, K. S.
Van Loo, P.
Dive, C.
Lin, C. J.
Rabinowitz, M.
Aerts, H. J. W. L.
Hackshaw, A.
Shaw, J. A.
Zimmermann, B. G.
TRACERx consortium
PEACE consortium
Swanton, C.
First Published: 26-Apr-2017
Publisher: Nature Publishing Group
Citation: Nature, 2017, 545 (7655), pp. 446-451
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.
DOI Link: 10.1038/nature22364
eISSN: 1476-4687
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2017, Nature Publishing Group. Deposited with reference to the publisher’s open access archiving policy. (
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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