화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Nature, Vol.545, No.7655, 446-+, 2017
DOI10.1038/nature22364  Export Citation
Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution
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
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.