The evolution of non-small cell lung cancer metastases in TRACERx.
The evolution of non-small cell lung cancer metastases in TRACERx.
复制标题
DOI：
10.1038/s41586-023-05729-x
复制
发表时间：
2023-04
期刊：
影响因子：
64.8
通讯作者：
Thomas, Mathew
中科院分区：
文献类型：
--
作者：
Al Bakir, Maise;Huebner, Ariana;Martinez-Ruiz, Carlos;Grigoriadis, Kristiana;Watkins, Thomas B. K.;Pich, Oriol;Moore, David A.;Veeriah, Selvaraju;Ward, Sophia;Laycock, Joanne;Johnson, Diana;Rowan, Andrew;Razaq, Maryam;Akther, Mita;Naceur-Lombardelli, Cristina;Prymas, Paulina;Toncheva, Antonia;Hessey, Sonya;Dietzen, Michelle;Colliver, Emma;Frankell, Alexander;Bunkum, Abigail;Lim, Emilia L.;Karasaki, Takahiro;Abbosh, Christopher;Hiley, Crispin T.;Hill, Mark S.;Cook, Daniel E.;Wilson, Gareth A.;Salgado, Roberto;Nye, Emma;Stone, Richard Kevin;Fennell, Dean A.;Price, Gillian;Kerr, Keith M.;Naidu, Babu;Middleton, Gary;Summers, Yvonne;Lindsay, Colin R.;Blackhall, Fiona H.;Cave, Judith;Blyth, Kevin G.;Nair, Arjun;Ahmed, Asia;Taylor, Magali N.;Procter, Alexander James;Falzon, Mary;Lawrence, David;Navani, Neal;Thakrar, Ricky M.;Janes, Sam M.;Papadatos-Pastos, Dionysis;Forster, Martin D.;Lee, Siow Ming;Ahmad, Tanya;Quezada, Sergio;Peggs, Karl S.;Van Loo, Peter;Dive, Caroline;Hackshaw, Allan;Birkbak, Nicolai J.;Zaccaria, Simone;Jamal-Hanjani, Mariam;McGranahan, Nicholas;Swanton, Charles;Lester, Jason F.;Bajaj, Amrita;Nakas, Apostolos;Sodha-Ramdeen, Azmina;Ang, Keng;Tufail, Mohamad;Chowdhry, Mohammed Fiyaz;Scotland, Molly;Boyles, Rebecca;Rathinam, Sridhar;Wilson, Claire;Marrone, Domenic;Dulloo, Sean;Matharu, Gurdeep;Shaw, Jacqui A.;Riley, Joan;Primrose, Lindsay;Boleti, Ekaterini;Cheyne, Heather;Khalil, Mohammed;Richardson, Shirley;Cruickshank, Tracey;Benafif, Sarah;Gilbert, Kayleigh;Patel, Akshay J.;Osman, Aya;Lacson, Christer;Langman, Gerald;Shackleford, Helen;Djearaman, Madava;Kadiri, Salma;Leek, Angela;Hodgkinson, Jack Davies;Totten, Nicola;Montero, Angeles;Smith, Elaine;Fontaine, Eustace;Granato, Felice;Doran, Helen;Novasio, Juliette;Rammohan, Kendadai;Joseph, Leena;Bishop, Paul;Shah, Rajesh;Moss, Stuart;Joshi, Vijay;Crosbie, Philip;Gomes, Fabio;Brown, Kate;Carter, Mathew;Chaturvedi, Anshuman;Priest, Lynsey;Oliveira, Pedro;Krebs, Matthew G.;Clipson, Alexandra;Tugwood, Jonathan;Kerr, Alastair;Rothwell, Dominic G.;Kilgour, Elaine;Aerts, Hugo J. W. L.;Schwarz, Roland F.;Kaufmann, Tom L.;Rosenthal, Rachel;Szallasi, Zoltan;Kisistok, Judit;Sokac, Mateo;Diossy, Miklos;Demeulemeester, Jonas;Stewart, Aengus;Magness, Alastair;Karamani, Angeliki;Chain, Benny;Campbell, Brittany B.;Castignani, Carla;Bailey, Chris;Puttick, Clare;Weeden, Clare E.;Lee, Claudia;Richard, Corentin;Pearce, David R.;Karagianni, Despoina;Biswas, Dhruva;Levi, Dina;Hoxha, Elena;Larose Cadieux, Elizabeth;Gronroos, Eva;Galvez-Cancino, Felip;Athanasopoulou, Foteini;Gimeno-Valiente, Francisco;Kassiotis, George;Stavrou, Georgia;Mastrokalos, Gerasimos;Zhai, Haoran;Lowe, Helen L.;Matos, Ignacio;Goldman, Jacki;Reading, James L.;Black, James R. M.;Herrero, Javier;Rane, Jayant K.;Nicod, Jerome;Lam, Jie Min;Hartley, John A.;Enfield, Katey S. S.;Selvaraju, Kayalvizhi;Thol, Kerstin;Litchfield, Kevin;Ng, Kevin W.;Chen, Kezhong;Dijkstra, Krijn;Thakkar, Krupa;Ensell, Leah;Shah, Mansi;Vasquez, Marcos;Litovchenko, Maria;Werner Sunderland, Mariana;Leung, Michelle;Escudero, Mickael;Angelova, Mihaela;Tanic, Miljana;Sivakumar, Monica;Kanu, Nnennaya;Chervova, Olga;Lucas, Olivia;Al-Sawaf, Othman;Hobson, Philip;Pawlik, Piotr;Bentham, Robert;Hynds, Robert E.;Vendramin, Roberto;Saghafinia, Sadegh;Lopez, Saioa;Gamble, Samuel;Ung, Seng Kuong Anakin;Vanloo, Sharon;Boeing, Stefan;Beck, Stephan;Bola, Supreet Kaur;Denner, Tamara;Marafioti, Teresa;Mourikis, Thanos P.;Spanswick, Victoria;Barbe, Vittorio;Lu, Wei-Ting;Hill, William;Liu, Wing Kin;Wu, Yin;Naito, Yutaka;Ramsden, Zoe;Veiga, Catarina;Royle, Gary;Collins-Fekete, Charles-Antoine;Fraioli, Francesco;Ashford, Paul;Clark, Tristan;Borg, Elaine;Wilson, James;Patrini, Davide;Martinoni Hoogenboom, Emilie;Monk, Fleur;Holding, James W.;Choudhary, Junaid;Bhakhri, Kunal;Scarci, Marco;Hayward, Martin;Panagiotopoulos, Nikolaos;Gorman, Pat;Khiroya, Reena;Stephens, Robert C. M.;Wong, Yien Ning Sophia;Bandula, Steve;Sharp, Abigail;Smith, Sean;Gower, Nicole;Dhanda, Harjot Kaur;Chan, Kitty;Pilotti, Camilla;Leslie, Rachel;Grapa, Anca;Zhang, Hanyun;AbdulJabbar, Khalid;Pan, Xiaoxi;Yuan, Yinyin;Chuter, David;MacKenzie, Mairead;Chee, Serena;Alzetani, Aiman;Scarlett, Lydia;Richards, Jennifer;Ingram, Papawadee;Austin, Silvia;Lim, Eric;De Sousa, Paulo;Jordan, Simon;Rice, Alexandra;Raubenheimer, Hilgardt;Bhayani, Harshil;Ambrose, Lyn;Devaraj, Anand;Chavan, Hema;Begum, Sofina;Buderi, Silviu, I;Kaniu, Daniel;Malima, Mpho;Booth, Sarah;Nicholson, Andrew G.;Fernandes, Nadia;Shah, Pratibha;Proli, Chiara;Hewish, Madeleine;Danson, Sarah;Shackcloth, Michael J.;Robinson, Lily;Russell, Peter;Dick, Craig;Le Quesne, John;Kirk, Alan;Asif, Mo;Bilancia, Rocco;Kostoulas, Nikos;Thomas, Mathew
转移性疾病是大多数癌症相关死亡的原因。我们报告了TRACERx前瞻性招募的421例发生转移性疾病的患者中126例非小细胞肺癌（NSCLC）肿瘤的纵向演变分析，并与144例非转移性肿瘤的对照队列进行了比较。在25%的病例中，转移灶在原发性肿瘤的最后一次克隆扫描之前早期分化，并且在初次诊断时吸烟的患者中早期分化较丰富。模拟结果表明，早期转移的分歧更经常发生在较小的肿瘤直径（小于8毫米）。单区域原发性肿瘤采样导致83%的晚期分歧病例被错误分类为早期，突出了广泛的原发性肿瘤采样的重要性。32%的病例发现多克隆传播与胸外疾病复发相关。在不到20%的病例中，原发性淋巴结疾病导致转移性复发，这代表了转移潜力的标志，而不是随后复发/疾病进展的途径。转移播种亚克隆表现出原发性肿瘤内的亚克隆扩增，可能反映了积极的选择。我们的研究结果强调了在未经治疗的原发性肿瘤中选择转移性克隆演变的重要性，单克隆与多克隆接种在决定复发部位方面的区别，目前放射学筛查方法对早期发散性肿瘤的局限性，以及需要制定针对复发前转移接种亚克隆的策略。对126例肺癌转移患者的纵向进化分析揭示了转移分化的时间、传播模式和转移过渡期间受选择的基因组事件。
Metastatic disease is responsible for the majority of cancer-related deaths. 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. A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.
登录
查看更多内容
影响因子：
64.8
作者：
Frankell, Alexander M.;Dietzen, Michelle;Al Bakir, Maise;Lim, Emilia L.;Karasaki, Takahiro;Ward, Sophia;Veeriah, Selvaraju;Colliver, Emma;Huebner, Ariana;Bunkum, Abigail;Hill, Mark S.;Grigoriadis, Kristiana;Moore, David A.;Black, James R. M.;Liu, Wing Kin;Thol, Kerstin;Pich, Oriol;Watkins, Thomas B. K.;Naceur-Lombardelli, Cristina;Cook, Daniel E.;Salgado, Roberto;Wilson, Gareth A.;Bailey, Chris;Angelova, Mihaela;Bentham, Robert;Martinez-Ruiz, Carlos;Abbosh, Christopher;Nicholson, Andrew G.;Le Quesne, John;Biswas, Dhruva;Rosenthal, Rachel;Puttick, Clare;Hessey, Sonya;Lee, Claudia;Prymas, Paulina;Toncheva, Antonia;Smith, Jon;Xing, Wei;Nicod, Jerome;Price, Gillian;Kerr, Keith M.;Naidu, Babu;Middleton, Gary;Blyth, Kevin G.;Fennell, Dean A.;Forster, Martin D.;Lee, Siow Ming;Falzon, Mary;Hewish, Madeleine;Shackcloth, Michael J.;Lim, Eric;Benafif, Sarah;Russell, Peter;Boleti, Ekaterini;Krebs, Matthew G.;Lester, Jason F.;Papadatos-Pastos, Dionysis;Ahmad, Tanya;Thakrar, Ricky M.;Lawrence, David;Navani, Neal;Janes, Sam M.;Dive, Caroline;Blackhall, Fiona H.;Summers, Yvonne;Cave, Judith;Marafioti, Teresa;Herrero, Javier;Quezada, Sergio A.;Peggs, Karl S.;Schwarz, Roland F.;Van Loo, Peter;Miedema, Daniel M.;Birkbak, Nicolai J.;Hiley, Crispin T.;Hackshaw, Allan;Zaccaria, Simone;Jamal-Hanjani, Mariam;McGranahan, Nicholas;Swanton, Charles;Bajaj, Amrita;Nakas, Apostolos;Sodha-Ramdeen, Azmina;Ang, Keng;Tufail, Mohamad;Chowdhry, Mohammed Fiyaz;Scotland, Molly;Boyles, Rebecca;Rathinam, Sridhar;Wilson, Claire;Marrone, Domenic;Dulloo, Sean;Matharu, Gurdeep;Shaw, Jacqui A.;Riley, Joa;Primrose, Lindsay;Cheyne, Heather;Khalil, Mohammed;Richardson, Shirley;Cruickshank, Tracey;Gilbert, Kayleigh;Patel, Akshay J.;Osman, Aya;Lacson, Christer;Langman, Gerald;Shackleford, Helen;Djearaman, Madava;Kadiri, Salma;Leek, Angela;Hodgkinson, Jack Davies;Totten, Nicola;Montero, Angeles;Smith, Elaine;Fontaine, Eustace;Granato, Felice;Doran, Helen;Novasio, Juliette;Rammohan, Kendadai;Joseph, Leena;Bishop, Paul;Shah, Rajesh;Moss, Stuart;Joshi, Vijay;Crosbie, Philip;Gomes, Fabio;Brown, Kate;Carter, Mathew;Chaturvedi, Anshuman;Priest, Lynsey;Oliveira, Pedro;Lindsay, Colin R.;Clipson, Alexandra;Tugwood, Jonathan;Kerr, Alastair;Rothwell, Dominic G.;Kilgour, Elaine;Aerts, Hugo J. W. L.;Kaufmann, Tom L.;Szallasi, Zoltan;Kisistok, Judit;Sokac, Mateo;Diossy, Miklos;Demeulemeester, Jonas;Stewart, Aengus;Magness, Alastair;Rowan, Andrew;Karamani, Angeliki;Chain, Benny;Campbell, Brittany B.;Castignani, Carla;Weeden, Clare E.;Richard, Corentin;Pearce, David R.;Karagianni, Despoina;Levi, Dina;Hoxha, Elena;Larose Cadieux, Elizabeth;Nye, Emma;Gronroos, Eva;Galvez-Cancino, Felip;Athanasopoulou, Foteini;Gimeno-Valiente, Francisco;Kassiotis, George;Stavrou, Georgia;Mastrokalos, Gerasimos;Zhai, Haoran L.;Lowe, Helen L.;Matos, Ignacio;Goldman, Jacki;Reading, James L.;Rane, Jayant K.;Lam, Jie Min;Hartley, John A.;Enfield, Katey S. S.;Selvaraju, Kayalvizhi;Litchfield, Kevin;Ng, Kevin W.;Chen, Kezhong;Dijkstra, Krijn;Thakkar, Krupa;Ensell, Leah;Shah, Mansi;Vasquez, Marcos;Litovchenko, Maria;Werner Sunderland, Mariana;Leung, Michelle;Escudero, Mickael;Tanic, Miljana;Sivakumar, Monica;Kanu, Nnennaya;Chervova, Olga;Lucas, Olivia;Al-Sawaf, Othman;Hobson, Philip;Pawlik, Piotr;Stone, Richard Kevin;Hynds, Robert E.;Vendramin, Roberto;Saghafinia, Sadegh;Lopez, Saioa;Gamble, Samuel;Ung, Seng Kuong Anakin;Vanloo, Sharon;Boeing, Stefan;Beck, Stephan;Bola, Supreet Kaur;Denner, Tamara;Mourikis, Thanos P.;Spanswick, Victoria;Barbe, Vittorio;Lu, Wei-Ting;Hill, William;Wu, Yin;Naito, Yutaka;Ramsden, Zoe;Veiga, Catarina;Royle, Gary;Collins-Fekete, Charles-Antoine;Fraioli, Francesco;Ashford, Paul;Clark, Tristan;Borg, Elaine;Wilson, James;Procter, Alexander James;Ahmed, Asia;Taylor, Magali N.;Nair, Arjun;Patrini, Davide;Martinoni Hoogenboom, Emilie;Monk, Fleur;Holding, James W.;Choudhary, Junaid;Bhakhri, Kunal;Scarci, Marco;Hayward, Martin;Panagiotopoulos, Nikolaos;Gorman, Pat;Khiroya, Reena;Stephens, Robert C. M.;Wong, Yien Ning Sophia;Bandula, Steve;Sharp, Abigail;Smith, Sean;Gower, Nicole;Dhanda, Harjot Kaur;Chan, Kitty;Pilotti, Camilla;Leslie, Rachel;Grapa, Anca;Zhang, Hanyun;AbdulJabbar, Khalid;Pan, Xiaoxi;Yuan, Yinyin;Chuter, David;MacKenzie, Mairead;Chee, Serena;Alzetani, Aiman;Scarlett, Lydia;Richards, Jennifer;Ingram, Papawadee;Austin, Silvia;De Sousa, Paulo;Jordan, Simon;Rice, Alexandra;Raubenheimer, Hilgardt;Bhayani, Harshil;Ambrose, Lyn;Devaraj, Anand;Chavan, Hema;Begum, Sofina;Buderi, Silviu, I;Kaniu, Daniel;Malima, Mpho;Booth, Sarah;Fernandes, Nadia;Shah, Pratibha;Proli, Chiara;Danson, Sarah;Robinson, Lily;Dick, Craig;Kirk, Alan;Asif, Mo;Bilancia, Rocco;Kostoulas, Nikos;Thomas, Mathew
通讯作者：
Thomas, Mathew
影响因子：
7
作者：
Boot A;Huang MN;Ng AWT;Ho SC;Lim JQ;Kawakami Y;Chayama K;Teh BT;Nakagawa H;Rozen SG
通讯作者：
Rozen SG
影响因子：
50.3
作者：
Berger AH;Brooks AN;Wu X;Shrestha Y;Chouinard C;Piccioni F;Bagul M;Kamburov A;Imielinski M;Hogstrom L;Zhu C;Yang X;Pantel S;Sakai R;Watson J;Kaplan N;Campbell JD;Singh S;Root DE;Narayan R;Natoli T;Lahr DL;Tirosh I;Tamayo P;Getz G;Wong B;Doench J;Subramanian A;Golub TR;Meyerson M;Boehm JS
通讯作者：
Boehm JS
影响因子：
64.8
作者：
Abbosh C;Frankell AM;Harrison T;Kisistok J;Garnett A;Johnson L;Veeriah S;Moreau M;Chesh A;Chaunzwa TL;Weiss J;Schroeder MR;Ward S;Grigoriadis K;Shahpurwalla A;Litchfield K;Puttick C;Biswas D;Karasaki T;Black JRM;Martínez-Ruiz C;Bakir MA;Pich O;Watkins TBK;Lim EL;Huebner A;Moore DA;Godin-Heymann N;L'Hernault A;Bye H;Odell A;Roberts P;Gomes F;Patel AJ;Manzano E;Hiley CT;Carey N;Riley J;Cook DE;Hodgson D;Stetson D;Barrett JC;Kortlever RM;Evan GI;Hackshaw A;Daber RD;Shaw JA;Aerts HJWL;Licon A;Stahl J;Jamal-Hanjani M;TRACERx Consortium;Birkbak NJ;McGranahan N;Swanton C
通讯作者：
Swanton C
影响因子：
5.5
作者：
Bueno, Juliana;Landeras, Luis;Chung, Jonathan H.
通讯作者：
Chung, Jonathan H.