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Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

Abbosh, Christopher, Birkbak, Nicolai J., Wilson, Gareth A., Jamal-Hanjani, Mariam, Constantin, Tudor, Salari, Raheleh, Quesne, John Le, 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, Bakir, Maise Al, 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, Quinn, Anne Marie, Crosbie, Phil, 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, 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, Van Loo, Peter, Dive, Caroline, Lin, C. Jimmy, Rabinowitz, Matthew, Aerts, Hugo JWL, Hackshaw, Allan, Shaw, Jacqui A, Zimmermann, Bernhard G., Swanton, Charles, Jamal-Hanjani, Mariam, Abbosh, Christopher, Veeriah, Selvaraju, Shafi, Seema, Czyzewska-Khan, Justyna, Johnson, Diana, Laycock, Joanne, Bosshard-Carter, Leticia, Goh, Gerald, Rosenthal, Rachel, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E, Wilson, Gareth, Birkbak, Nicolai J, Watkins, Thomas B K, McGranahan, Nicholas, Horswell, Stuart, Al Bakir, Maise, GrÖnroos, Eva, Mitter, Richard, Escudero, Mickael, Stewart, Aengus, Van Loo, Peter, Rowan, Andrew, Xu, Hang, Turajlic, Samra, Hiley, Crispin, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Matthews, Nik, Elgar, Greg, Ward, Sophia, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Chambers, Tim, Nye, Emma, Graca, Sofia, Al Bakir, Maise, Joshi, Kroopa, Furness, Andrew, Aissa, Assma Ben, Wong, Yien Ning Sophia, Georgiou, Andy, Quezada, Sergio, Hartley, John A, Lowe, Helen L, Herrero, Javier, Lawrence, David, Hayward, Martin, Panagiotopoulos, Nikolaos, Kolvekar, Shyam, Falzon, Mary, Borg, Elaine, Marafioti, Teresa, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Oukrif, Dahmane, Akarca, Ayse U, Janes, Sam M, Thakrar, Ricky, Forster, Martin, Ahmad, Tanya, Lee, Siow Ming, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Ahmed, Asia, Taylor, Magali, Choudhary, Junaid, Summers, Yvonne, Califano, Raffaele, Taylor, Paul, Shah, Rajesh, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Crosbie, Phil, Moss, Stuart, Idries, Faiza, Joseph, Leena, Bishop, Paul, Chaturved, Anshuman, Marie Quinn, Anne, Doran, Helen, leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Blackhall, Fiona, Rogan, Jane, Smith, Elaine, Dive, Caroline, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G, Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Naidu, Babu, Langman, Gerald, Trotter, Simon, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Middleton, Gary, Djearaman, Madava, Fennell, Dean, Shaw, Jacqui A, Le Quesne, John, Moore, David, Thomas, Anne, Walter, Harriet, Riley, Joan, Martinson, Luke, Nakas, Apostolos, Rathinam, Sridhar, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Riley, Joan, Primrose, Lindsay, Martinson, Luke, Anand, Girija, Khan, Sajid, Amadi, Anita, Nicolson, Marianne, Kerr, Keith, Palmer, Shirley, Remmen, Hardy, Miller, Joy, Buchan, Keith, Chetty, Mahendran, Gomersall, Lesley, Lester, Jason, Edwards, Alison, Morgan, Fiona, Adams, Haydn, Davies, Helen, Kornaszewska, Malgorzata, Attanoos, Richard, Lock, Sara, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Bell, Harriet, Iles, Natasha, Hackshaw, Allan, Ngai, Yenting, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Tavares Barbosa, Monica, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Elena Cufari, Maria, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G, Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Ezhil, Veni, Ismail, Babikir, Irvin-sellers, Melanie, Prakash, Vineet, Russell, Peter, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Constatin, Tudor, Salari, Raheleh, Sponer, Nicole, Naik, Ashwini, Zimmermann, Bernhard, Rabinowitz, Matthew, Aerts, Hugo J. W. L., Dentro, Stefan, Dessimoz, Christophe, Swanton, Charles, Jamal-Hanjani, Mariam, Abbosh, Christopher, Shiu, Kai-Keen, Bridgewater, John, Hochauser, Daniel, Van Loo, Peter, Quezada, Sergio, Beck, Stephan, Parker, Peter, Walczak, Henning, Enver, Tariq, Falzon, Mary, Proctor, Ian, Sinclair, Ron, Lok, Chi-wah, Novelli, Marco, Marafioti, Teresa, Borg, Elaine, Mitchison, Miriam, Trevisan, Giorgia, Lynch, Mark, Brandner, Sebastian, Gishen, Faye, Tookman, Adrian, Stone, Paddy, Sterling, Caroline, Larkin, James, Turajlic, Samra, Attard, Gert, Eeles, Ros, Foster, Chris, Bova, Steve, Sottoriva, Andrea, Chowdhury, Simon, Ashish, Chandra, Spicer, James, Stares, Mark, Lynch, Joanna, Caldas, Carlos, Brenton, James, Fitzgerald, Rebecca, Jimenez-Linan, Merche, Provenzano, Elena, Cluroe, Alison, Stewart, Grant, Watts, Colin, Gilbertson, Richard, McDermott, Ultan, Tavare, Simon, Maughan, Tim, Tomlinson, Ian, Campbell, Peter, McNeish, Iain, Biankin, Andrew, Chambers, Antony, Fraser, Sioban, Oien, Karin, Krebs, Matt, Blackhall, Fiona, Summers, Yvonne, Dive, Caroline, Marais, Richard, Carter, Louise, Nonaka, Daisuke, Quinn, Anne Marie, Dhomen, Nathalie, Fennell, Dean, Le Quesne, John, Moore, David, Shaw, Jacqui, Naidu, Babu, Baijal, Shobhit, Tanchel, Bruce, Langman, Gerald, Collard, Martin, Cockcroft, Peter, Taylor, Joanne, Bancroft, Hollie, Kerr, Amy, Middleton, Gary, Webb, Joanne, Kadiri, Salma, Colloby, Peter, Olisemeke, Bernard, Wilson, Rodelaine, Ottensmeier, Christian, Harrison, David, Loda, Massimo, Flanagan, Adreinne, Wilcox, Maggie, McKenzie, Mairead, Hackshaw, Allan, Lederman, Jonathan, Sharp, Abby, Farrelly, Laura and Swanton, Charles 2017. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution. Nature 545 (7655) , pp. 446-451. 10.1038/nature22364

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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

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Nature Publishing Group
ISSN: 0028-0836
Date of First Compliant Deposit: 2 May 2017
Date of Acceptance: 13 April 2017
Last Modified: 12 Aug 2019 15:41
URI: http://orca-mwe.cf.ac.uk/id/eprint/100264

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