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Cited by 1,874

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Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Open access
The TRACERx consortium, Abbosh, Christopher, The PEACE consortium, Birkbak, Nicolai J., Wilson, Gareth A., Jamal-Hanjani, Mariam, Constantin, Tudor, Salari, Raheleh, Le Quesne, John, Moore, David A., Veeriah, Selvaraju, Rosenthal, Rachel, Marafioti, Teresa, Kirkizlar, Eser, Watkins, Thomas B. K., McGranahan, Nicholas, Ward, Sophia, Martinson, Luke, Riley, Joan, Fraioli, Francesco, Al Bakir, Maise, Grönroos, Eva, Zambrana, Francisco, Endozo, Raymondo, Bi, Wenya Linda, Fennessy, Fiona M., Sponer, Nicole, Johnson, Diana, Laycock, Joanne, Shafi, Seema, Czyzewska-Khan, Justyna, Rowan, Andrew, Chambers, Tim, Matthews, Nik, Turajlic, Samra, Hiley, Crispin, Lee, Siow Ming, Forster, Martin D., Ahmad, Tanya, Falzon, Mary, Borg, Elaine, Lawrence, David, Hayward, Martin, Kolvekar, Shyam, Panagiotopoulos, Nikolaos, Janes, Sam M., Thakrar, Ricky, Ahmed, Asia, Blackhall, Fiona, Summers, Yvonne, Hafez, Dina, Naik, Ashwini, Ganguly, Apratim, Kareht, Stephanie, Shah, Rajesh, Joseph, Leena, Marie Quinn, Anne, Crosbie, Phil A., Naidu, Babu, Middleton, Gary, Langman, Gerald, Trotter, Simon, Nicolson, Marianne, Remmen, Hardy, Kerr, Keith, Chetty, Mahendran, Gomersall, Lesley, Fennell, Dean A., Nakas, Apostolos, Rathinam, Sridhar, Anand, Girija, Khan, Sajid, Russell, Peter, Ezhil, Veni, Ismail, Babikir, Irvin-Sellers, Melanie, Prakash, Vineet, Lester, Jason F., Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Oukrif, Dahmane, Akarca, Ayse U., Hartley, John A., Lowe, Helen L., Lock, Sara, Iles, Natasha, Bell, Harriet, Ngai, Yenting, Elgar, Greg, Szallasi, Zoltan, Schwarz, Roland F., Herrero, Javier, Stewart, Aengus, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Lin, C. Jimmy, Rabinowitz, Matthew, Aerts, Hugo J. W. L., Hackshaw, Allan, Shaw, Jacqui A., Zimmermann, Bernhard G., Swanton, Charles·2017·Nature

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.

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Authors
The TRACERx consortium, Abbosh, C., The PEACE consortium, 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., 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., & Swanton, C.
Venue
Nature
Published
2017-04-26
Volume
545
Issue
7655
Pages
446-451
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2608738563
Cited by
1,874
References
7
FWCI
48.30
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. https://app.cochat.ai/papers/10.1038/nature22364
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The TRACERx consortium, Abbosh, C., The PEACE consortium, 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., . . . Swanton, C. (2017). Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. https://doi.org/10.1038/nature22364

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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