Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

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Item Type:	Article
Title:	Phylogenetic ctDNA analysis depicts early stage lung cancer evolution
Creators Name:	Abbosh, C., Birkbak, N.J., Wilson, G.A., Jamal-Hanjani, M., Constantin, T., Salari, R., Quesne, J.L., 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., Bakir, M.A., 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., Quinn, A.M., Crosbie, P., 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., Van Loo, P., Dive, C., Lin, C.J., Rabinowitz, M., Aerts, H.J.W.L., Hackshaw, A., Shaw, J.A., 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
Volume:	545
Number:	7655
Page Range:	446-451
Date:	25 May 2017
Additional Information:	Erratum in: Nature (2017) doi: 10.1038/nature25161 [epub ahead of print]
Official Publication:	https://doi.org/10.1038/nature22364
External Fulltext:	View full text on PubMed Central Europe
PubMed:	View item in PubMed

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