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Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

Abbosh, Christopher and Birkbak, Nicolai J and Wilson, Gareth A and Jamal-Hanjani, Mariam and Constantin, Tudor and Salari, Raheleh and Le Quesne, John and Moore, David A and Veeriah, Selvaraju and Rosenthal, Rachel and Marafioti, Teresa and Kirkizlar, Eser and Watkins, Thomas B K and McGranahan, Nicholas and Ward, Sophia and Martinson, Luke and Riley, Joan and Fraioli, Francesco and Al Bakir, Maise and Grönroos, Eva and Zambrana, Francisco and Endozo, Raymondo and Bi, Wenya Linda and Fennessy, Fiona M and Sponer, Nicole and Johnson, Diana and Laycock, Joanne and Shafi, Seema and Czyzewska-Khan, Justyna and Rowan, Andrew and Chambers, Tim and Matthews, Nik and Turajlic, Samra and Hiley, Crispin and Lee, Siow Ming and Forster, Martin D and Ahmad, Tanya and Falzon, Mary and Borg, Elaine and Lawrence, David and Hayward, Martin and Kolvekar, Shyam and Panagiotopoulos, Nikolaos and Janes, Sam M and Thakrar, Ricky and Ahmed, Asia and Blackhall, Fiona and Summers, Yvonne and Hafez, Dina and Naik, Ashwini and Ganguly, Apratim and Kareht, Stephanie and Shah, Rajesh and Joseph, Leena and Marie Quinn, Anne and Crosbie, Phil A and Naidu, Babu V and Middleton, Gary and Langman, Gerald and Trotter, Simon and Nicolson, Marianne and Remmen, Hardy and Kerr, Keith and Chetty, Mahendran and Gomersall, Lesley and Fennell, Dean A and Nakas, Apostolos and Rathinam, Sridhar and Anand, Girija and Khan, Sajid and Russell, Peter and Ezhil, Veni and Ismail, Babikir and Irvin-Sellers, Melanie and Prakash, Vineet and Lester, Jason F and Kornaszewska, Malgorzata and Attanoos, Richard and Adams, Haydn and Davies, Helen and Oukrif, Dahmane and Akarca, Ayse U and Hartley, John A and Lowe, Helen L and Lock, Sara and Iles, Natasha and Bell, Harriet and Ngai, Yenting and Elgar, Greg and Szallasi, Zoltan and Schwarz, Roland F and Herrero, Javier and Stewart, Aengus and Quezada, Sergio A and Peggs, Karl S and Van Loo, Peter and Dive, Caroline and Lin, C Jimmy and Rabinowitz, Matthew and Aerts, Hugo J W L and Hackshaw, Allan and Shaw, Jacqui A and Zimmermann, Bernhard G and Swanton, Charles (2017) Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature, 545 (7655). pp. 446-451. ISSN 1476-4687. This article is available to all HEFT staff and students via ASK HEFT Discovery tool http://tinyurl.com/z795c8c using their HEFT Athens Login.

Full text not available from this repository.
Official URL: https://www.nature.com/articles/nature22364

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: Article
Additional Information: This article is available to all HEFT staff and students via ASK HEFT Discovery tool http://tinyurl.com/z795c8c using their HEFT Athens Login.
Subjects: QZ Pathology. Oncology
WG Cardiovascular system. Cardiology
Divisions: Clinical Support > Pathology
Emergency Services > Cardiology
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Depositing User: Mr Philip O'Reilly
Date Deposited: 28 Nov 2017 14:22
Last Modified: 28 Nov 2017 14:22
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1542

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