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Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution
| File | Description | Size | Format | |
|---|---|---|---|---|
 Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.pdf | Accepted version | 5.69 MB | Adobe PDF | View/Open |
| Title: | Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution |
| Authors: | Abbosh, C Birkbak, NJ Wilson, GA Jamal-Hanjani, M Constantin, T Salari, R Le Quesne, J Moore, DA Veeriah, S Rosenthal, R Marafioti, T Kirkizlar, E Watkins, TBK McGranahan, N Ward, S Martinson, L Riley, J Fraioli, F Al Bakir, M Gronroos, E Zambrana, F Endozo, R Bi, WL Fennessy, FM Sponer, N Johnson, D Laycock, J Shafi, S Czyzewska-Khan, J Rowan, A Chambers, T Matthews, N Turajlic, S Hiley, C Lee, SM Forster, MD Ahmad, T Falzon, M Borg, E Lawrence, D Hayward, M Kolvekar, S Panagiotopoulos, N Janes, SM Thakrar, R Ahmed, A Blackhall, F Summers, Y Hafez, D Naik, A Ganguly, A Kareht, S Shah, R Joseph, L Quinn, AM Crosbie, PA Naidu, B Middleton, G Langman, G Trotter, S Nicolson, M Remmen, H Kerr, K Chetty, M Gomersall, L Fennell, DA Nakas, A Rathinam, S Anand, G Khan, S Russell, P Ezhil, V Ismail, B Irvin-Sellers, M Prakash, V Lester, JF Kornaszewska, M Attanoos, R Adams, H Davies, H Oukrif, D Akarca, AU Hartley, JA Lowe, HL Lock, S Iles, N Bell, H Ngai, Y Elgar, G Szallasi, Z Schwarz, RF Herrero, J Stewart, A Quezada, SA Peggs, KS Van Loo, P Dive, C Lin, CJ Rabinowitz, M Aerts, HJWL Hackshaw, A Shaw, JA Zimmermann, BG Swanton, C Jamal-Hanjani, M Abbosh, C Veeriah, S Shafi, S Czyzewska-Khan, J Johnson, D Laycock, J Bosshard-Carter, L Goh, G Rosenthal, R Gorman, P Murugaesu, N Hynds, RE Wilson, GA Birkbak, NJ Watkins, TBK McGranahan, N Horswell, S Al Bakir, M Gronroos, E Mitter, R Escudero, M Stewart, A Van Loo, P Rowan, A Xu, H Turajlic, S Hiley, C Goldman, J Stone, RK Denner, T Matthews, N Elgar, G Ward, S Biggs, J Costa, M Begum, S Phillimore, B Chambers, T Nye, E Graca, S Joshi, K Furness, A Ben Aissa, A Wong, YNS Georgiou, A Quezada, SA Peggs, KS Hartley, JA Lowe, HL Herrero, J Lawrence, D Hayward, M Panagiotopoulos, N Kolvekar, S Falzon, M Borg, E Marafioti, T Simeon, C Hector, G Smith, A Aranda, M Novelli, M Oukrif, D Akarca, AU Janes, SM Thakrar, R Forster, MD Ahmad, T Lee, SM Papadatos-Pastos, D Carnell, D Mendes, R George, J Navani, N Ahmed, A Taylor, M Choudhary, J Summers, Y Califano, R Taylor, P Shah, R Krysiak, P Rammohan, K Fontaine, E Booton, R Evison, M Crosbie, PA Moss, S Idries, F Joseph, L Bishop, P Chaturvedi, A Quinn, AM Doran, H Leek, A Harrison, P Moore, K Waddington, R Novasio, J Blackhall, F Rogan, J Smith, E Dive, C Tugwood, J Brady, G Rothwell, DG Chemi, F Pierce, J Gulati, S Naidu, B Langman, G Trotter, S Bellamy, M Bancroft, H Kerr, A Kadiri, S Webb, J Middleton, G Djearaman, M Fennell, DA Shaw, JA Le Quesne, J Moore, DA Thomas, A Walter, H Riley, J Martinson, L Nakas, A Rathinam, S Monteiro, W Marshall, H Nelson, L Bennett, J Primrose, L Anand, G Khan, S Amadi, A Nicolson, M Kerr, K Palmer, S Remmen, H Miller, J Buchan, K Chetty, M Gomersall, L Lester, JF Edwards, A Morgan, F Adams, H Davies, H Kornaszewska, M Attanoos, R Lock, S Verjee, A MacKenzie, M Wilcox, M Bell, H Iles, N Hackshaw, A Ngai, Y Smith, S Gower, N Ottensmeier, C Chee, S Johnson, B Alzetani, A Shaw, E Lim, E De Sousa, P Barbosa, MT Bowman, A Jordan, S Rice, A Raubenheimer, H Proli, C Cufari, ME Ronquillo, JC Kwayie, A Bhayani, H Hamilton, M Bakar, Y Mensah, N Ambrose, L Devaraj, A Buderi, S Finch, J Azcarate, L Chavan, H Green, S Mashinga, H Nicholson, AG Lau, K Sheaff, M Schmid, P Conibear, J Ezhil, V Ismail, B Irvin-Sellers, M Prakash, V Russell, P Light, T Horey, T Danson, S Bury, J Edwards, J Hill, J Matthews, S Kitsanta, Y Suvarna, K Fisher, P Keerio, AD Shackcloth, M Gosney, J Postmus, P Feeney, S Asante-Siaw, J Constantin, T Salari, R Sponer, N Naik, A Zimmermann, BG Rabinowitz, M Aerts, HJWL Dentro, S Dessimoz, C |
| Item Type: | Journal Article |
| 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. |
| Issue Date: | 25-May-2017 |
| Date of Acceptance: | 13-Apr-2017 |
| URI: | http://hdl.handle.net/10044/1/61406 |
| DOI: | https://dx.doi.org/10.1038/nature22364 |
| ISSN: | 0028-0836 |
| Publisher: | NATURE PUBLISHING GROUP |
| Start Page: | 446 |
| End Page: | 451 |
| Journal / Book Title: | NATURE |
| Volume: | 545 |
| Copyright Statement: | © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. The final publication is available at https://dx.doi.org/10.1038/nature22364 |
| Keywords: | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics CIRCULATING TUMOR DNA NEGATIVE BREAST-CANCER UPTAKE RATIO FDG PET STATISTICS MUTATIONS CARCINOMA IMPACT Biopsy Carcinoma, Non-Small-Cell Lung Cell Lineage Cell Tracking Clone Cells DNA Mutational Analysis DNA, Neoplasm Disease Progression Drug Resistance, Neoplasm Early Detection of Cancer Evolution, Molecular Humans Limit of Detection Lung Neoplasms Multiplex Polymerase Chain Reaction Neoplasm Metastasis Neoplasm Recurrence, Local Postoperative Care Reproducibility of Results Tumor Burden TRACERx consortium PEACE consortium MD Multidisciplinary General Science & Technology |
| Publication Status: | Published |
| Online Publication Date: | 2017-04-26 |
| Appears in Collections: | Department of Surgery and Cancer |