The evolution of non-small cell lung cancer metastases in TRACERx

被引：116

作者：

Al Bakir, Maise ^{[1
,2
]}

Huebner, Ariana ^{[1
,2
,3
]}

Martinez-Ruiz, Carlos ^{[1
,3
]}

Grigoriadis, Kristiana ^{[1
,2
,3
]}

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

Pich, Oriol ^{[2
]}

Moore, David A. ^{[1
,2
,4
]}

Veeriah, Selvaraju ^{[1
]}

Ward, Sophia ^{[1
,2
,5
]}

Laycock, Joanne ^{[1
]}

Johnson, Diana ^{[1
]}

Rowan, Andrew ^{[2
]}

Razaq, Maryam ^{[1
]}

Akther, Mita ^{[1
]}

Naceur-Lombardelli, Cristina ^{[1
]}

Prymas, Paulina ^{[1
]}

Toncheva, Antonia ^{[1
]}

Hessey, Sonya ^{[1
,6
,7
]}

Dietzen, Michelle ^{[1
,2
,3
]}

Colliver, Emma ^{[2
]}

Frankell, Alexander ^{[1
,2
]}

Bunkum, Abigail ^{[1
,6
,7
]}

Lim, Emilia L. ^{[1
,2
]}

Karasaki, Takahiro ^{[1
,2
,6
]}

Abbosh, Christopher ^{[1
]}

Hiley, Crispin T. ^{[1
,2
]}

Hill, Mark S. ^{[2
]}

Cook, Daniel E. ^{[2
]}

Wilson, Gareth A. ^{[2
]}

Salgado, Roberto ^{[8
,9
]}

Nye, Emma ^{[10
]}

Stone, Richard Kevin ^{[10
]}

Fennell, Dean A. ^{[11
,12
]}

Price, Gillian ^{[13
,14
]}

Kerr, Keith M. ^{[14
,15
]}

Naidu, Babu ^{[16
]}

Middleton, Gary ^{[17
,18
]}

Summers, Yvonne ^{[19
,20
]}

Lindsay, Colin R. ^{[19
,20
]}

Blackhall, Fiona H. ^{[19
,20
]}

Cave, Judith ^{[21
]}

Blyth, Kevin G. ^{[22
,23
,24
]}

Nair, Arjun ^{[25
,26
]}

Ahmed, Asia ^{[25
]}

Taylor, Magali N. ^{[25
]}

Procter, Alexander James ^{[25
]}

Falzon, Mary ^{[4
]}

Lawrence, David ^{[27
]}

Navani, Neal ^{[28
,29
]}

Thakrar, Ricky M. ^{[28
,29
]}

机构：

[1] UCL, Inst Canc, Canc Res UK Lung Canc Ctr Excellence, London, England

[2] Francis Crick Inst, Canc Evolut & Genome Instabil Lab, London, England

[3] UCL, Inst Canc, Canc Genome Evolut Res Grp, Canc Res UK Lung Canc Ctr Excellence, London, England

[4] Univ Coll London Hosp, Dept Cellular Pathol, London, England

[5] Francis Crick Inst, Adv Sequencing Facil, London, England

[6] UCL, Canc Metastasis Lab, Inst Canc, London, England

[7] UCL, Computat Canc Genom Res Grp, Inst Canc, London, England

[8] ZAS Hosp, Dept Pathol, Antwerp, Belgium

[9] Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic, Australia

[10] Francis Crick Inst, Expt Histopathol, London, England

[11] Univ Leicester, Leicester, Leics, England

[12] Univ Hosp Leicester NHS Trust, Leicester, Leics, England

[13] Aberdeen Royal Infirm NHS Grampian, Dept Med Oncol, Aberdeen, Scotland

[14] Univ Aberdeen, Aberdeen, Scotland

[15] Aberdeen Royal Infirm NHS Grampian, Dept Pathol, Aberdeen, Scotland

[16] Univ Birmingham, Birmingham Acute Care Res Grp, Inst Inflammat & Ageing, Birmingham, W Midlands, England

[17] Univ Hosp Birmingham NHS Fdn Trust, Birmingham, W Midlands, England

[18] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England

[19] Univ Manchester, Div Canc Sci, Manchester, Lancs, England

[20] Christie NHS Fdn Trust, Manchester, Lancs, England

[21] Univ Hosp Southampton NHS Fdn Trust, Dept Oncol, Southampton, Hants, England

[22] Univ Glasgow, Sch Canc Sci, Glasgow, Lanark, Scotland

[23] Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland

[24] Queen Elizabeth Univ Hosp, Glasgow, Lanark, Scotland

[25] Univ Coll London Hosp, Dept Radiol, London, England

[26] UCL, Dept Med, UCL Resp, London, England

[27] Univ Coll London Hosp NHS Trust, Dept Thorac Surg, London, England

[28] UCL, Lungs Living Res Ctr, UCL Resp, London, England

[29] Univ Coll London Hosp, Dept Thorac Med, London, England

[30] Univ Coll London Hosp, Dept Oncol, London, England

[31] UCL, Inst Canc, Immune Regulat & Tumour Immunotherapy Grp, Canc Immunol Unit,Res Dept Haematol, London, England

[32] Univ Coll London Hosp, Dept Haematol, London, England

[33] UCL, Inst Canc, Canc Immunol Unit, Dept Res Haematol, London, England

[34] Francis Crick Inst, Canc Genom Lab, London, England

[35] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX USA

[36] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX USA

[37] Univ Manchester, Canc Res UK Manchester Inst Canc Biomarker Ctr, Manchester, Lancs, England

[38] Univ Manchester, Canc Res UK Lung Canc Ctr Excellence, Manchester, Lancs, England

[39] Canc Res UK, London, England

[40] UCL Canc Trials Ctr, London, England

[41] Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark

[42] Aarhus Univ, Dept Clin Med, Aarhus, Denmark

[43] Aarhus Univ, Bioinformat Res Ctr, Aarhus, Denmark

[44] Swansea Bay Univ Hlth Board, Singleton Hosp, Swansea, W Glam, Wales

[45] Univ Leicester, Ctr Canc Res, Leicester, Leics, England

[46] Royal Free London NHS Fdn Trust, Royal Free Hosp, London, England

[47] Aberdeen Royal Infirm NHS Grampian, Aberdeen, Scotland

[48] Whittington Hosp NHS Trust, London, England

[49] Manchester Canc Res Ctr Biobank, Manchester, Lancs, England

[50] Manchester Univ NHS Fdn Trust, Wythenshawe Hosp, Wythenshawe, England

来源：

NATURE | 2023年 / 616卷 / 7957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：

SOCIETY GUIDELINES; PULMONARY NODULES; TRACKING; INSTABILITY; SELECTION; ORIGINS; HISTORY; DRIVER;

D O I：

10.1038/s41586-023-05729-x

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：

Metastatic disease is responsible for the majority of cancer-related deaths(1). We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.

引用

页码：534 / +

页数：34

共 63 条

[1] Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA [J].

Abbosh, Christopher ;

Frankell, Alexander ;

Harrison, Thomas ;

Kisistok, Judit ;

Garnett, Aaron ;

Johnson, Laura ;

Veeriah, Selvaraju ;

Moreau, Mike ;

Chesh, Adrian ;

Chaunzwa, Tafadzwa ;

Weiss, Jakob ;

Schroeder, Morgan ;

Ward, Sophia ;

Grigoriadis, Kristiana ;

Shahpurwalla, Aamir ;

Litchfield, Kevin ;

Puttick, Clare ;

Biswas, Dhruva ;

Karasaki, Takahiro ;

Black, James R. M. ;

Martinez-Ruiz, Carlos ;

Al Bakir, Maise ;

Pich, Oriol ;

Watkins, Thomas B. K. ;

Lim, Emilia ;

Huebner, Ariana ;

Moore, David I. ;

Godin-Heymann, Nadia ;

L'Hernault, Anne ;

Bye, Hannah ;

Odell, Aaron G. ;

Roberts, Paula ;

Gomes, Fabio ;

Patel, Akshay ;

Manzano, Elizabeth ;

Hiley, Crispin ;

Carey, Nicolas J. ;

Riley, Joan ;

Cook, Daniel ;

Hodgson, Darren G. ;

Stetson, Daniel ;

Barrett, J. Carl ;

Kortlever, Roderik ;

Evan, Gerard ;

Hackshaw, Allan ;

Daber, Robert ;

Shaw, Jacqui ;

Aerts, Hugo J. W. L. J. ;

Licon, Abel ;

Stahl, Josh .

NATURE, 2023, 616 (7957) :553-+

[2] Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution [J].

Abbosh, Christopher ;

Birkbak, Nicolai J. ;

Wilson, Gareth A. ;

Jamal-Hanjani, Mariam ;

Constantin, Tudor ;

Salari, Raheleh ;

Le Quesne, John ;

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 ;

Al Bakir, Maise ;

Gronroos, 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 .

NATURE, 2017, 545 (7655) :446-+

[3] The repertoire of mutational signatures in human cancer [J].

Alexandrov, Ludmil B. ;

Kim, Jaegil ;

Haradhvala, Nicholas J. ;

Huang, Mi Ni ;

Ng, Alvin Wei Tian ;

Wu, Yang ;

Boot, Arnoud ;

Covington, Kyle R. ;

Gordenin, Dmitry A. ;

Bergstrom, Erik N. ;

Islam, S. M. Ashiqul ;

Lopez-Bigas, Nuria ;

Klimczak, Leszek J. ;

McPherson, John R. ;

Morganella, Sandro ;

Sabarinathan, Radhakrishnan ;

Wheeler, David A. ;

Mustonen, Ville ;

Getz, Gad ;

Rozen, Steven G. ;

Stratton, Michael R. .

NATURE, 2020, 578 (7793) :94-+

[4]

American College of Radiology Committee on Lung-RADS, 2019, Lung-RADS assessment categories

[5] Tracking Cancer Evolution through the Disease Course [J].

Bailey, Chris ;

Black, James R. M. ;

Reading, James L. ;

Litchfield, Kevin ;

Turajlic, Samra ;

McGranahan, Nicholas ;

Jamal-Hanjani, Mariam ;

Swanton, Charles .

CANCER DISCOVERY, 2021, 11 (04) :916-932

[6]

Bailey MH, 2018, CELL, V173, P371, DOI [10.1016/j.cell.2018.02.060, 10.1016/j.cell.2018.07.034]

[7] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[8] High-throughput Phenotyping of Lung Cancer Somatic Mutations [J].

Berger, Alice H. ;

Brooks, Angela N. ;

Wu, Xiaoyun ;

Shrestha, Yashaswi ;

Chouinard, Candace ;

Piccioni, Federica ;

Bagul, Mukta ;

Kamburov, Atanas ;

Imielinski, Marcin ;

Hogstrom, Larson ;

Zhu, Cong ;

Yang, Xiaoping ;

Pantel, Sasha ;

Sakai, Ryo ;

Watson, Jacqueline ;

Kaplan, Nathan ;

Campbell, Joshua D. ;

Singh, Shantanu ;

Root, David E. ;

Narayan, Rajiv ;

Natoli, Ted ;

Lahr, David L. ;

Tirosh, Itay ;

Tamayo, Pablo ;

Getz, Gad ;

Wong, Bang ;

Doench, John ;

Subramanian, Aravind ;

Golub, Todd R. ;

Meyerson, Matthew ;

Boehm, Jesse S. .

CANCER CELL, 2016, 30 (02) :214-228

[9] In-depth characterization of the cisplatin mutational signature in human cell lines and in esophageal and liver tumors [J].

Boot, Arnoud ;

Huang, Mi Ni ;

Ng, Alvin W. T. ;

Ho, Szu-Chi ;

Lim, Jing Quan ;

Kawakami, Yoshiiku ;

Chayama, Kazuaki ;

Teh, Bin Tean ;

Nakagawa, Hidewaki ;

Rozen, Steven G. .

GENOME RESEARCH, 2018, 28 (05) :654-665

[10] Accumulation of driver and passenger mutations during tumor progression [J].

Bozic, Ivana ;

Antal, Tibor ;

Ohtsuki, Hisashi ;

Carter, Hannah ;

Kim, Dewey ;

Chen, Sining ;

Karchin, Rachel ;

Kinzler, Kenneth W. ;

Bogelstein, Bert ;

Nowak, Martin A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (43) :18545-18550

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