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Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

Item Type:Article
Title:Phylogenetic ctDNA analysis depicts early stage lung cancer evolution
Creators Name:Abbosh, C. and Birkbak, N.J. and Wilson, G.A. and Jamal-Hanjani, M. and Constantin, T. and Salari, R. and Quesne, J.L. and Moore, D.A. and Veeriah, S. and Rosenthal, R. and Marafioti, T. and Kirkizlar, E. and Watkins, T.B.K. and McGranahan, N. and Ward, S. and Martinson, L. and Riley, J. and Fraioli, F. and Bakir, M.A. and Groenroos, E. and Zambrana, F. and Endozo, R. and Bi, W.L. and Fennessy, F.M. and Sponer, N. and Johnson, D. and Laycock, J. and Shafi, S. and Czyzewska-Khan, J. and Rowan, A. and Chambers, T. and Matthews, N. and Turajlic, S. and Hiley, C. and Lee, S.M. and Forster, M.D. and Ahmad, T. and Falzon, M. and Borg, E. and Lawrence, D. and Hayward, M. and Kolvekar, S. and Panagiotopoulos, N. and Janes, S.M. and Thakrar, R. and Ahmed, A. and Blackhall, F. and Summers, Y. and Hafez, D. and Naik, A. and Ganguly, A. and Kareht, S. and Shah, R. and Joseph, L. and Quinn, A.M. and Crosbie, P. and Naidu, B. and Middleton, G. and Langman, G. and Trotter, S. and Nicolson, M. and Remmen, H. and Kerr, K. and Chetty, M. and Gomersall, L. and Fennell, D.A. and Nakas, A. and Rathinam, S. and Anand, G. and Khan, S. and Russell, P. and Ezhil, V. and Ismail, B. and Irvin-Sellers, M. and Prakash, V. and Lester, J.F. and Kornaszewska, M. and Attanoos, R. and Adams, H. and Davies, H. and Oukrif, D. and Akarca, A.U. and Hartley, J.A. and Lowe, H.L. and Lock, S. and Iles, N. and Bell, H. and Ngai, Y. and Elgar, G. and Szallasi, Z. and Schwarz, R.F. and Herrero, J. and Stewart, A. and Quezada, S.A. and Van Loo, P. and Dive, C. and Lin, C.J. and Rabinowitz, M. and Aerts, H.J.W.L. and Hackshaw, A. and Shaw, J.A. and Zimmermann, B.G. and Swanton, C.
Abstract:The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies.
Keywords:Biopsy, Cell Lineage, Cell Tracking, Clone Cells, DNA Mutational Analysis, Disease Progression, Early Detection of Cancer, Limit of Detection, Local Neoplasm Recurrence, Lung Neoplasms, Molecular Evolution, Multiplex Polymerase Chain Reaction, Neoplasm DNA, Neoplasm Drug Resistance, Neoplasm Metastasis, Non-Small-Cell Lung Carcinoma, Postoperative Care, Reproducibility of Results, Tumor Burden
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:545
Number:7655
Page Range:446-451
Date:25 May 2017
Official Publication:https://doi.org/10.1038/nature22364
PubMed:View item in PubMed

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