Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

被引：1363

作者：

Abbosh, Christopher ^{[1
]}

Birkbak, Nicolai J. ^{[1
,2
]}

Wilson, Gareth A. ^{[1
,2
]}

Jamal-Hanjani, Mariam ^{[1
]}

Constantin, Tudor ^{[3
]}

Salari, Raheleh ^{[3
]}

Le Quesne, John ^{[4
]}

Moore, David A. ^{[4
]}

Veeriah, Selvaraju ^{[1
]}

Rosenthal, Rachel ^{[1
]}

Marafioti, Teresa ^{[1
,5
]}

Kirkizlar, Eser ^{[3
]}

Watkins, Thomas B. K. ^{[1
,2
]}

McGranahan, Nicholas ^{[1
,2
]}

Ward, Sophia ^{[1
,2
,6
]}

Martinson, Luke ^{[4
]}

Riley, Joan ^{[4
]}

Fraioli, Francesco ^{[7
]}

Al Bakir, Maise ^{[2
]}

Gronroos, Eva ^{[2
]}

Zambrana, Francisco ^{[1
]}

Endozo, Raymondo ^{[7
]}

Bi, Wenya Linda ^{[8
,9
]}

Fennessy, Fiona M. ^{[8
,9
]}

Sponer, Nicole ^{[3
]}

Johnson, Diana ^{[1
]}

Laycock, Joanne ^{[1
]}

Shafi, Seema ^{[1
]}

Czyzewska-Khan, Justyna ^{[1
]}

Rowan, Andrew ^{[2
]}

Chambers, Tim ^{[2
,6
]}

Matthews, Nik ^{[6
,10
]}

Turajlic, Samra ^{[2
,11
,12
]}

Hiley, Crispin ^{[1
,2
]}

Lee, Siow Ming ^{[1
,13
]}

Forster, Martin D. ^{[1
,13
]}

Ahmad, Tanya ^{[13
]}

Falzon, Mary ^{[5
]}

Borg, Elaine ^{[5
]}

Lawrence, David ^{[14
]}

Hayward, Martin ^{[14
]}

Kolvekar, Shyam ^{[14
]}

Panagiotopoulos, Nikolaos ^{[14
]}

Janes, Sam M. ^{[1
,15
,16
]}

Thakrar, Ricky ^{[15
]}

Ahmed, Asia ^{[17
]}

Blackhall, Fiona ^{[18
,19
]}

Summers, Yvonne ^{[19
]}

Hafez, Dina ^{[3
]}

Naik, Ashwini ^{[3
]}

机构：

[1] UCL, Canc Inst, Canc Res UK Lung Canc Ctr Excellence London & Man, Paul OGorman Bldg,72 Huntley St, London WC1E 6DD, England

[2] Francis Crick Inst, Translat Canc Therapeut Lab, 1 Midland Rd, London NW1 1AT, England

[3] Natera Inc, 201 Ind Rd, San Carlos, CA 94070 USA

[4] Univ Leicester, Canc Studies, Leicester LE2 7LX, Leics, England

[5] Univ Coll London Hosp, Dept Pathol, 21 Univ St, London WC1 6JJ, England

[6] Francis Crick Inst, Adv Sequencing Facil, 1 Midland Rd, London NW1 1AT, England

[7] Univ Coll London Hosp, Dept Nucl Med, 235 Euston Rd, London NW1 2BU, England

[8] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[9] Harvard Med Sch, Boston, MA 02115 USA

[10] Inst Canc Res, Tumour Profiling Unit, Genom Facil, 237 Fulham Rd, London SW3 6JB, England

[11] Royal Marsden Hosp, Renal Unit, London SW3, England

[12] Royal Marsden Hosp, Skin Unit, London SW3, England

[13] Univ Coll London Hosp, Dept Oncol, 250 Euston Rd, London NW1 2BU, England

[14] Univ Coll London Hosp, Dept Cardiothorac Surg, 235 Euston Rd, London NW1 2BU, England

[15] Univ Coll London Hosp, Dept Resp Med, 235 Euston Rd, London NW1 2BU, England

[16] UCL, Div Med, Lungs Living Res Ctr, UCL Resp, Rayne Bldg,5 Univ St, London WC1E 6JF, England

[17] Univ Coll London Hosp, Dept Radiol, 235 Euston Rd, London NW1 2BU, England

[18] Univ Manchester, Inst Canc Studies, Oxford Rd, Manchester M13 9PL, Lancs, England

[19] Christie Hosp, Manchester M20 4BX, Lancs, England

[20] Univ Hosp South Manchester, Dept Cardiothorac Surg, Manchester M23 9LT, Lancs, England

[21] Univ Hosp South Manchester, Dept Pathol, Manchester M23 9LT, Lancs, England

[22] Univ Hosp South Manchester, North West Lung Ctr, Manchester M23 9LT, Lancs, England

[23] Birmingham Heartlands Hosp, Dept Thorac Surg, Birmingham B9 5SS, W Midlands, England

[24] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England

[25] Birmingham Heartlands Hosp, Dept Cellular Pathol, Birmingham B9 5SS, W Midlands, England

[26] Univ Aberdeen, Dept Med Oncol, Med Sch, Aberdeen AB25 2ZN, Scotland

[27] Aberdeen Royal Infirm, Aberdeen AB25 2ZN, Scotland

[28] Univ Aberdeen, Dept Cardiothorac Surg, Med Sch, Aberdeen AB25 2ZD, Scotland

[29] Aberdeen Royal Infirm, Aberdeen AB25 2ZD, Scotland

[30] Univ Aberdeen, Dept Pathol, Med Sch, Aberdeen AB25 2ZD, Scotland

[31] Univ Aberdeen, Dept Resp Med, Med Sch, Aberdeen AB25 2ZN, Scotland

[32] Univ Aberdeen, Dept Radiol, Med Sch, Aberdeen AB25 2ZN, Scotland

[33] Glenfield Hosp, Dept Thorac Surg, Leicester LE3 9QP, Leics, England

[34] North Middlesex Univ Hosp, Dept Radiotherapy, London N18, England

[35] Royal Free Hosp, Dept Resp Med, Pond St, London NW3 2QG, England

[36] Barnet Hosp, Dept Resp Med, Wellhouse Lane, Barnet EN5 3DJ, England

[37] Chase Farm Hosp, Dept Resp Med, Wellhouse Lane, Barnet EN5 3DJ, England

[38] Princess Alexandra Hosp, Dept Resp Med, Hamstel Rd, Harlow CM20 1QX, Essex, England

[39] Royal Surrey Cty Hosp, St Lukes Canc Ctr, Dept Clin Oncol, Guildford GU2 7XX, Surrey, England

[40] Ashford & St Peters Hosp, Dept Pathol, Guildford Rd, Chertsey KT16 0PZ, Surrey, England

[41] Ashford & St Peters Hosp, Dept Resp Med, Guildford Rd, Chertsey KT16 0PZ, Surrey, England

[42] Ashford & St Peters Hosp, Dept Radiol, Guildford Rd, Chertsey KT16 0PZ, Surrey, England

[43] Velindre Hosp, Dept Clin Oncol, Cardiff CF14 2TL, S Glam, Wales

[44] Univ Hosp Wales, Dept Cardiothorac Surg, Cardiff CF14 4XW, S Glam, Wales

[45] Univ Hosp Wales, Dept Cellular Pathol, Heath Pk, Cardiff, S Glam, Wales

[46] Cardiff Univ, Heath Pk, Cardiff, S Glam, Wales

[47] Univ Hosp Llandough, Dept Radiol, Cardiff CF64 2XX, S Glam, Wales

[48] Univ Hosp Llandough, Dept Resp Med, Cardiff CF64 2XX, S Glam, Wales

[49] UCL, Expt Canc Med Ctr, GCLP Facil, Canc Inst, Paul OGorman Bldg,72 Huntley St, London WC1E 6DD, England

[50] Whittington Hosp NHS Trust, Dept Resp Med, London N19 5NF, England

来源：

NATURE | 2017年 / 545卷 / 7655期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

CIRCULATING TUMOR DNA; UPTAKE RATIO; MUTATIONS; IMPACT;

D O I：

10.1038/nature22364

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：446 / +

页数：21

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