Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Abbosh, C. et al. (2017) Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature, 545(7655), pp. 446-451. (doi: 10.1038/nature22364) (PMID:28445469) (PMCID:PMC5812436)

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.

• Item Type: Articles
• Additional Information: Authors, and TRACERx Consortium ; PEACE Consortium.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Le Quesne, Professor John and Oien, Professor Karin
• Authors: Abbosh, C., Birkbak, N. J., Wilson, G. A., Jamal-Hanjani, M., Constantin, T., Salari, R., Le Quesne, J., 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., Quinn, A. M., 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., and Swanton, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature
• Publisher: Nature Research
• ISSN: 0028-0836
• ISSN (Online): 1476-4687
• Published Online: 26 April 2017
• Copyright Holders: Copyright © 2017 Macmillan Publishers Limited, part of Springer Nature
• First Published: First published in Nature 545(7655): 446-451
• Publisher Policy: Reproduced in accordance with the publisher copyright policy