The evolution of lung cancer and impact of subclonal selection in TRACERx.
The evolution of lung cancer and impact of subclonal selection in TRACERx.
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DOI：
10.1038/s41586-023-05783-5
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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：
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
肺癌是全球癌症相关死亡率的主要原因。在这里，我们分析了从前瞻性入组TRACERx研究的前421名非小细胞肺癌患者中在手术或随访期间取样的1，644个肿瘤区域。该项目旨在破译肺癌演变并解决主要研究终点：确定肿瘤内异质性与临床结局之间的关系。在肺腺癌中，40种常见癌症基因中有22种突变处于显著的亚克隆选择下，包括经典的肿瘤起始基因如TP53和KRAS。我们定义了驱动程序，突变过程和全基因组加倍（WGD）事件之间的进化依赖关系。尽管患者有吸烟史，但8%的肺腺癌缺乏烟草诱导突变的证据。与从不吸烟者的肿瘤相比，这些肿瘤的EGFR突变和RET、ROS1、ALK和MET致癌亚型的检出率也相似，这表明它们具有相似的病因学和发病机制。大的亚克隆扩增与阳性亚克隆选择相关。在系统发育分支的末端，肿瘤最近发生亚克隆扩增的患者，无病生存期明显较短。在19%的肿瘤中检测到亚克隆WGD，并且10%的肿瘤平行地具有多个亚克隆WGD。亚克隆，而不是干，WGD与较短的无病生存期。拷贝数异质性与术后1年内胸外复发相关。这些数据证明了克隆扩增、WGD和拷贝数不稳定性在确定非小细胞肺癌复发的时间和模式方面的重要性，并提供了全面的临床癌症演变数据资源。对前瞻性入组TRACERx研究的421例非小细胞肺癌患者的多区域肿瘤样本进行分析，揭示了肿瘤演变的决定因素以及肿瘤内异质性与临床结局之间的关系。
Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource. Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.
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DOI：
10.1093/annonc/mdu479
发表时间：
2015-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Favero F;Joshi T;Marquard AM;Birkbak NJ;Krzystanek M;Li Q;Szallasi Z;Eklund AC
通讯作者：
Eklund AC
影响因子：
64.8
作者：
Burrell RA;McClelland SE;Endesfelder D;Groth P;Weller MC;Shaikh N;Domingo E;Kanu N;Dewhurst SM;Gronroos E;Chew SK;Rowan AJ;Schenk A;Sheffer M;Howell M;Kschischo M;Behrens A;Helleday T;Bartek J;Tomlinson IP;Swanton C
通讯作者：
Swanton C
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：
8.8
作者：
BERENBLUM, I;SHUBIK, P
通讯作者：
SHUBIK, P
影响因子：
14.9
作者：
Costello M;Pugh TJ;Fennell TJ;Stewart C;Lichtenstein L;Meldrim JC;Fostel JL;Friedrich DC;Perrin D;Dionne D;Kim S;Gabriel SB;Lander ES;Fisher S;Getz G
通讯作者：
Getz G