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158 results on '"Grönroos, Eva"'

1. The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

Author

Caswell, Deborah R, Gui, Philippe, Mayekar, Manasi K, Law, Emily K, Pich, Oriol, Bailey, Chris, Boumelha, Jesse, Kerr, D Lucas, Blakely, Collin M, Manabe, Tadashi, Martinez-Ruiz, Carlos, Bakker, Bjorn, De Dios Palomino Villcas, Juan, I. Vokes, Natalie, Dietzen, Michelle, Angelova, Mihaela, Gini, Beatrice, Tamaki, Whitney, Allegakoen, Paul, Wu, Wei, Humpton, Timothy J, Hill, William, Tomaschko, Mona, Lu, Wei-Ting, Haderk, Franziska, Al Bakir, Maise, Nagano, Ai, Gimeno-Valiente, Francisco, de Carné Trécesson, Sophie, Vendramin, Roberto, Barbè, Vittorio, Mugabo, Miriam, Weeden, Clare E, Rowan, Andrew, McCoach, Caroline E, Almeida, Bruna, Green, Mary, Gomez, Carlos, Nanjo, Shigeki, Barbosa, Dora, Moore, Chris, Przewrocka, Joanna, Black, James RM, Grönroos, Eva, Suarez-Bonnet, Alejandro, Priestnall, Simon L, Zverev, Caroline, Lighterness, Scott, Cormack, James, Olivas, Victor, Cech, Lauren, Andrews, Trisha, Rule, Brandon, Jiao, Yuwei, Zhang, Xinzhu, Ashford, Paul, Durfee, Cameron, Venkatesan, Subramanian, Temiz, Nuri Alpay, Tan, Lisa, Larson, Lindsay K, Argyris, Prokopios P, Brown, William L, Yu, Elizabeth A, Rotow, Julia K, Guha, Udayan, Roper, Nitin, Yu, Johnny, Vogel, Rachel I, Thomas, Nicholas J, Marra, Antonio, Selenica, Pier, Yu, Helena, Bakhoum, Samuel F, Chew, Su Kit, Reis-Filho, Jorge S, Jamal-Hanjani, Mariam, Vousden, Karen H, McGranahan, Nicholas, Van Allen, Eliezer M, Kanu, Nnennaya, Harris, Reuben S, Downward, Julian, Bivona, Trever G, and Swanton, Charles

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Bioinformatics and Computational Biology, Genetics, Agricultural Biotechnology, Biotechnology, Lung Cancer, Lung, Cancer, Women's Health, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Humans, Animals, Mice, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Mutation, Up-Regulation, ErbB Receptors, Cytidine Deaminase, Minor Histocompatibility Antigens, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.

Published
2024

2. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Author

Hobor, Sebastijan, Al Bakir, Maise, Hiley, Crispin T., Skrzypski, Marcin, Frankell, Alexander M., Bakker, Bjorn, Watkins, Thomas B. K., Markovets, Aleksandra, Dry, Jonathan R., Brown, Andrew P., van der Aart, Jasper, van den Bos, Hilda, Spierings, Diana, Oukrif, Dahmane, Novelli, Marco, Chakrabarti, Turja, Rabinowitz, Adam H., Ait Hassou, Laila, Litière, Saskia, Kerr, D. Lucas, Tan, Lisa, Kelly, Gavin, Moore, David A., Renshaw, Matthew J., Venkatesan, Subramanian, Hill, William, Huebner, Ariana, Martínez-Ruiz, Carlos, Black, James R. M., Wu, Wei, Angelova, Mihaela, McGranahan, Nicholas, Downward, Julian, Chmielecki, Juliann, Barrett, Carl, Litchfield, Kevin, Chew, Su Kit, Blakely, Collin M., de Bruin, Elza C., Foijer, Floris, Vousden, Karen H., Bivona, Trever G., Hynds, Robert E., Kanu, Nnennaya, Zaccaria, Simone, Grönroos, Eva, and Swanton, Charles

Published
2024
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3. Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models

Author

Hynds, Robert E., Huebner, Ariana, Pearce, David R., Hill, Mark S., Akarca, Ayse U., Moore, David A., Ward, Sophia, Gowers, Kate H. C., Karasaki, Takahiro, Al Bakir, Maise, Wilson, Gareth A., Pich, Oriol, Martínez-Ruiz, Carlos, Hossain, A. S. Md Mukarram, Pearce, Simon P., Sivakumar, Monica, Ben Aissa, Assma, Grönroos, Eva, Chandrasekharan, Deepak, Kolluri, Krishna K., Towns, Rebecca, Wang, Kaiwen, Cook, Daniel E., Bosshard-Carter, Leticia, Naceur-Lombardelli, Cristina, Rowan, Andrew J., Veeriah, Selvaraju, Litchfield, Kevin, Crosbie, Philip A. J., Dive, Caroline, Quezada, Sergio A., Janes, Sam M., Jamal-Hanjani, Mariam, Marafioti, Teresa, McGranahan, Nicholas, and Swanton, Charles

Published
2024
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4. Lung adenocarcinoma promotion by air pollutants

Author

Hill, William, Lim, Emilia L., Weeden, Clare E., Lee, Claudia, Augustine, Marcellus, Chen, Kezhong, Kuan, Feng-Che, Marongiu, Fabio, Evans, Jr, Edward J., Moore, David A., Rodrigues, Felipe S., Pich, Oriol, Bakker, Bjorn, Cha, Hongui, Myers, Renelle, van Maldegem, Febe, Boumelha, Jesse, Veeriah, Selvaraju, Rowan, Andrew, Naceur-Lombardelli, Cristina, Karasaki, Takahiro, Sivakumar, Monica, De, Swapnanil, Caswell, Deborah R., Nagano, Ai, Black, James R. M., Martínez-Ruiz, Carlos, Ryu, Min Hyung, Huff, Ryan D., Li, Shijia, Favé, Marie-Julie, Magness, Alastair, Suárez-Bonnet, Alejandro, Priestnall, Simon L., Lüchtenborg, Margreet, Lavelle, Katrina, Pethick, Joanna, Hardy, Steven, McRonald, Fiona E., Lin, Meng-Hung, Troccoli, Clara I., Ghosh, Moumita, Miller, York E., Merrick, Daniel T., Keith, Robert L., Al Bakir, Maise, Bailey, Chris, Hill, Mark S., Saal, Lao H., Chen, Yilun, George, Anthony M., Abbosh, Christopher, Kanu, Nnennaya, Lee, Se-Hoon, McGranahan, Nicholas, Berg, Christine D., Sasieni, Peter, Houlston, Richard, Turnbull, Clare, Lam, Stephen, Awadalla, Philip, Grönroos, Eva, Downward, Julian, Jacks, Tyler, Carlsten, Christopher, Malanchi, Ilaria, Hackshaw, Allan, Litchfield, Kevin, DeGregori, James, Jamal-Hanjani, Mariam, and Swanton, Charles

Published
2023
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5. Pervasive chromosomal instability and karyotype order in tumour evolution

Author

Watkins, Thomas BK, Lim, Emilia L, Petkovic, Marina, Elizalde, Sergi, Birkbak, Nicolai J, Wilson, Gareth A, Moore, David A, Grönroos, Eva, Rowan, Andrew, Dewhurst, Sally M, Demeulemeester, Jonas, Dentro, Stefan C, Horswell, Stuart, Au, Lewis, Haase, Kerstin, Escudero, Mickael, Rosenthal, Rachel, Bakir, Maise Al, Xu, Hang, Litchfield, Kevin, Lu, Wei Ting, Mourikis, Thanos P, Dietzen, Michelle, Spain, Lavinia, Cresswell, George D, Biswas, Dhruva, Lamy, Philippe, Nordentoft, Iver, Harbst, Katja, Castro-Giner, Francesc, Yates, Lucy R, Caramia, Franco, Jaulin, Fanny, Vicier, Cécile, Tomlinson, Ian PM, Brastianos, Priscilla K, Cho, Raymond J, Bastian, Boris C, Dyrskjøt, Lars, Jönsson, Göran B, Savas, Peter, Loi, Sherene, Campbell, Peter J, Andre, Fabrice, Luscombe, Nicholas M, Steeghs, Neeltje, Tjan-Heijnen, Vivianne CG, Szallasi, Zoltan, Turajlic, Samra, Jamal-Hanjani, Mariam, Van Loo, Peter, Bakhoum, Samuel F, Schwarz, Roland F, McGranahan, Nicholas, and Swanton, Charles

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Cancer, Human Genome, Chromosomal Instability, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 8, Clone Cells, Cyclin E, DNA Copy Number Variations, Evolution, Molecular, Female, Humans, Karyotype, Loss of Heterozygosity, Male, Mutagenesis, Neoplasm Metastasis, Neoplasms, Oncogene Proteins, General Science & Technology
Abstract

Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes1,2. The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation necessary for tumour evolution1,3,4. Here we use multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types to show that continuous chromosomal instability results in pervasive SCNA heterogeneity. Parallel evolutionary events, which cause disruption in the same genes (such as BCL9, MCL1, ARNT (also known as HIF1B), TERT and MYC) within separate subclones, were present in 37% of tumours. Most recurrent losses probably occurred before whole-genome doubling, that was found as a clonal event in 49% of tumours. However, loss of heterozygosity at the human leukocyte antigen (HLA) locus and loss of chromosome 8p to a single haploid copy recurred at substantial subclonal frequencies, even in tumours with whole-genome doubling, indicating ongoing karyotype remodelling. Focal amplifications that affected chromosomes 1q21 (which encompasses BCL9, MCL1 and ARNT), 5p15.33 (TERT), 11q13.3 (CCND1), 19q12 (CCNE1) and 8q24.1 (MYC) were frequently subclonal yet appeared to be clonal within single samples. Analysis of an independent series of 1,024 metastatic samples revealed that 13 focal SCNAs were enriched in metastatic samples, including gains in chromosome 8q24.1 (encompassing MYC) in clear cell renal cell carcinoma and chromosome 11q13.3 (encompassing CCND1) in HER2+ breast cancer. Chromosomal instability may enable the continuous selection of SCNAs, which are established as ordered events that often occur in parallel, throughout tumour evolution.

Published
2020

7. ALDH1L2 regulation of formate, formyl-methionine, and ROS controls cancer cell migration and metastasis

Author

Hennequart, Marc, primary, Pilley, Steven E., additional, Labuschagne, Christiaan F., additional, Coomes, Jack, additional, Mervant, Loic, additional, Driscoll, Paul C., additional, Legrave, Nathalie M., additional, Lee, Younghwan, additional, Kreuzaler, Peter, additional, Macintyre, Benedict, additional, Panina, Yulia, additional, Blagih, Julianna, additional, Stevenson, David, additional, Strathdee, Douglas, additional, Schneider-Luftman, Deborah, additional, Grönroos, Eva, additional, Cheung, Eric C., additional, Yuneva, Mariia, additional, Swanton, Charles, additional, and Vousden, Karen H., additional

Published
2023
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8. Supplementary Figure 7 from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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9. Data from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, primary, Puttick, Clare, primary, Zhai, Haoran, primary, Caswell, Deborah R., primary, Lu, Wei-Ting, primary, Dietzen, Michelle, primary, Galanos, Panagiotis, primary, Evangelou, Konstantinos, primary, Bellelli, Roberto, primary, Lim, Emilia L., primary, Watkins, Thomas B.K., primary, Rowan, Andrew, primary, Teixeira, Vitor H., primary, Zhao, Yue, primary, Chen, Haiquan, primary, Ngo, Bryan, primary, Zalmas, Lykourgos-Panagiotis, primary, Al Bakir, Maise, primary, Hobor, Sebastijan, primary, Grönroos, Eva, primary, Pennycuick, Adam, primary, Nigro, Ersilia, primary, Campbell, Brittany B., primary, Brown, William L., primary, Akarca, Ayse U., primary, Marafioti, Teresa, primary, Wu, Mary Y., primary, Howell, Michael, primary, Boulton, Simon J., primary, Bertoli, Cosetta, primary, Fenton, Tim R., primary, de Bruin, Robertus A.M., primary, Maya-Mendoza, Apolinar, primary, Santoni-Rugiu, Eric, primary, Hynds, Robert E., primary, Gorgoulis, Vassilis G., primary, Jamal-Hanjani, Mariam, primary, McGranahan, Nicholas, primary, Harris, Reuben S., primary, Janes, Sam M., primary, Bartkova, Jirina, primary, Bakhoum, Samuel F., primary, Bartek, Jiri, primary, Kanu, Nnennaya, primary, and Swanton, Charles, primary

Published
2023
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10. Supplementary Figure 3 from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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11. Supplementary Movie C from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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12. Supplementary Table 1 from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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13. Supplementary Figure 4 from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, primary, Puttick, Clare, primary, Zhai, Haoran, primary, Caswell, Deborah R., primary, Lu, Wei-Ting, primary, Dietzen, Michelle, primary, Galanos, Panagiotis, primary, Evangelou, Konstantinos, primary, Bellelli, Roberto, primary, Lim, Emilia L., primary, Watkins, Thomas B.K., primary, Rowan, Andrew, primary, Teixeira, Vitor H., primary, Zhao, Yue, primary, Chen, Haiquan, primary, Ngo, Bryan, primary, Zalmas, Lykourgos-Panagiotis, primary, Al Bakir, Maise, primary, Hobor, Sebastijan, primary, Grönroos, Eva, primary, Pennycuick, Adam, primary, Nigro, Ersilia, primary, Campbell, Brittany B., primary, Brown, William L., primary, Akarca, Ayse U., primary, Marafioti, Teresa, primary, Wu, Mary Y., primary, Howell, Michael, primary, Boulton, Simon J., primary, Bertoli, Cosetta, primary, Fenton, Tim R., primary, de Bruin, Robertus A.M., primary, Maya-Mendoza, Apolinar, primary, Santoni-Rugiu, Eric, primary, Hynds, Robert E., primary, Gorgoulis, Vassilis G., primary, Jamal-Hanjani, Mariam, primary, McGranahan, Nicholas, primary, Harris, Reuben S., primary, Janes, Sam M., primary, Bartkova, Jirina, primary, Bakhoum, Samuel F., primary, Bartek, Jiri, primary, Kanu, Nnennaya, primary, and Swanton, Charles, primary

Published
2023
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14. TRACERx Consortium Members from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, primary, Puttick, Clare, primary, Zhai, Haoran, primary, Caswell, Deborah R., primary, Lu, Wei-Ting, primary, Dietzen, Michelle, primary, Galanos, Panagiotis, primary, Evangelou, Konstantinos, primary, Bellelli, Roberto, primary, Lim, Emilia L., primary, Watkins, Thomas B.K., primary, Rowan, Andrew, primary, Teixeira, Vitor H., primary, Zhao, Yue, primary, Chen, Haiquan, primary, Ngo, Bryan, primary, Zalmas, Lykourgos-Panagiotis, primary, Al Bakir, Maise, primary, Hobor, Sebastijan, primary, Grönroos, Eva, primary, Pennycuick, Adam, primary, Nigro, Ersilia, primary, Campbell, Brittany B., primary, Brown, William L., primary, Akarca, Ayse U., primary, Marafioti, Teresa, primary, Wu, Mary Y., primary, Howell, Michael, primary, Boulton, Simon J., primary, Bertoli, Cosetta, primary, Fenton, Tim R., primary, de Bruin, Robertus A.M., primary, Maya-Mendoza, Apolinar, primary, Santoni-Rugiu, Eric, primary, Hynds, Robert E., primary, Gorgoulis, Vassilis G., primary, Jamal-Hanjani, Mariam, primary, McGranahan, Nicholas, primary, Harris, Reuben S., primary, Janes, Sam M., primary, Bartkova, Jirina, primary, Bakhoum, Samuel F., primary, Bartek, Jiri, primary, Kanu, Nnennaya, primary, and Swanton, Charles, primary

Published
2023
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15. Data from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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16. Supplementary Movie B from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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17. Supplementary Movie E from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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18. Supplementary Figure 2 from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, primary, Puttick, Clare, primary, Zhai, Haoran, primary, Caswell, Deborah R., primary, Lu, Wei-Ting, primary, Dietzen, Michelle, primary, Galanos, Panagiotis, primary, Evangelou, Konstantinos, primary, Bellelli, Roberto, primary, Lim, Emilia L., primary, Watkins, Thomas B.K., primary, Rowan, Andrew, primary, Teixeira, Vitor H., primary, Zhao, Yue, primary, Chen, Haiquan, primary, Ngo, Bryan, primary, Zalmas, Lykourgos-Panagiotis, primary, Al Bakir, Maise, primary, Hobor, Sebastijan, primary, Grönroos, Eva, primary, Pennycuick, Adam, primary, Nigro, Ersilia, primary, Campbell, Brittany B., primary, Brown, William L., primary, Akarca, Ayse U., primary, Marafioti, Teresa, primary, Wu, Mary Y., primary, Howell, Michael, primary, Boulton, Simon J., primary, Bertoli, Cosetta, primary, Fenton, Tim R., primary, de Bruin, Robertus A.M., primary, Maya-Mendoza, Apolinar, primary, Santoni-Rugiu, Eric, primary, Hynds, Robert E., primary, Gorgoulis, Vassilis G., primary, Jamal-Hanjani, Mariam, primary, McGranahan, Nicholas, primary, Harris, Reuben S., primary, Janes, Sam M., primary, Bartkova, Jirina, primary, Bakhoum, Samuel F., primary, Bartek, Jiri, primary, Kanu, Nnennaya, primary, and Swanton, Charles, primary

Published
2023
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19. Supplementary Figure 5 from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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20. Supplementary Movie D from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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21. Supplementary Movie A from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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22. Supplementary Figure 8 from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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23. Supplementary Table 2 from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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24. Supplementary Figure 1 from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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25. Supplementary Tables S1-S4 from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, primary, Puttick, Clare, primary, Zhai, Haoran, primary, Caswell, Deborah R., primary, Lu, Wei-Ting, primary, Dietzen, Michelle, primary, Galanos, Panagiotis, primary, Evangelou, Konstantinos, primary, Bellelli, Roberto, primary, Lim, Emilia L., primary, Watkins, Thomas B.K., primary, Rowan, Andrew, primary, Teixeira, Vitor H., primary, Zhao, Yue, primary, Chen, Haiquan, primary, Ngo, Bryan, primary, Zalmas, Lykourgos-Panagiotis, primary, Al Bakir, Maise, primary, Hobor, Sebastijan, primary, Grönroos, Eva, primary, Pennycuick, Adam, primary, Nigro, Ersilia, primary, Campbell, Brittany B., primary, Brown, William L., primary, Akarca, Ayse U., primary, Marafioti, Teresa, primary, Wu, Mary Y., primary, Howell, Michael, primary, Boulton, Simon J., primary, Bertoli, Cosetta, primary, Fenton, Tim R., primary, de Bruin, Robertus A.M., primary, Maya-Mendoza, Apolinar, primary, Santoni-Rugiu, Eric, primary, Hynds, Robert E., primary, Gorgoulis, Vassilis G., primary, Jamal-Hanjani, Mariam, primary, McGranahan, Nicholas, primary, Harris, Reuben S., primary, Janes, Sam M., primary, Bartkova, Jirina, primary, Bakhoum, Samuel F., primary, Bartek, Jiri, primary, Kanu, Nnennaya, primary, and Swanton, Charles, primary

Published
2023
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26. Supplementary Movie F from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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27. Supplementary Figure 3 from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, primary, Puttick, Clare, primary, Zhai, Haoran, primary, Caswell, Deborah R., primary, Lu, Wei-Ting, primary, Dietzen, Michelle, primary, Galanos, Panagiotis, primary, Evangelou, Konstantinos, primary, Bellelli, Roberto, primary, Lim, Emilia L., primary, Watkins, Thomas B.K., primary, Rowan, Andrew, primary, Teixeira, Vitor H., primary, Zhao, Yue, primary, Chen, Haiquan, primary, Ngo, Bryan, primary, Zalmas, Lykourgos-Panagiotis, primary, Al Bakir, Maise, primary, Hobor, Sebastijan, primary, Grönroos, Eva, primary, Pennycuick, Adam, primary, Nigro, Ersilia, primary, Campbell, Brittany B., primary, Brown, William L., primary, Akarca, Ayse U., primary, Marafioti, Teresa, primary, Wu, Mary Y., primary, Howell, Michael, primary, Boulton, Simon J., primary, Bertoli, Cosetta, primary, Fenton, Tim R., primary, de Bruin, Robertus A.M., primary, Maya-Mendoza, Apolinar, primary, Santoni-Rugiu, Eric, primary, Hynds, Robert E., primary, Gorgoulis, Vassilis G., primary, Jamal-Hanjani, Mariam, primary, McGranahan, Nicholas, primary, Harris, Reuben S., primary, Janes, Sam M., primary, Bartkova, Jirina, primary, Bakhoum, Samuel F., primary, Bartek, Jiri, primary, Kanu, Nnennaya, primary, and Swanton, Charles, primary

Published
2023
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28. Supplementary Figure 2 from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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29. Supplementary Figure 4 from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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30. Supplementary Figure 6 from Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, primary, Burrell, Rebecca A., primary, Rowan, Andrew J., primary, Grönroos, Eva, primary, Endesfelder, David, primary, Joshi, Tejal, primary, Mouradov, Dmitri, primary, Gibbs, Peter, primary, Ward, Robyn L., primary, Hawkins, Nicholas J., primary, Szallasi, Zoltan, primary, Sieber, Oliver M., primary, and Swanton, Charles, primary

Published
2023
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31. Supplementary Figure 1 from Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, primary, Puttick, Clare, primary, Zhai, Haoran, primary, Caswell, Deborah R., primary, Lu, Wei-Ting, primary, Dietzen, Michelle, primary, Galanos, Panagiotis, primary, Evangelou, Konstantinos, primary, Bellelli, Roberto, primary, Lim, Emilia L., primary, Watkins, Thomas B.K., primary, Rowan, Andrew, primary, Teixeira, Vitor H., primary, Zhao, Yue, primary, Chen, Haiquan, primary, Ngo, Bryan, primary, Zalmas, Lykourgos-Panagiotis, primary, Al Bakir, Maise, primary, Hobor, Sebastijan, primary, Grönroos, Eva, primary, Pennycuick, Adam, primary, Nigro, Ersilia, primary, Campbell, Brittany B., primary, Brown, William L., primary, Akarca, Ayse U., primary, Marafioti, Teresa, primary, Wu, Mary Y., primary, Howell, Michael, primary, Boulton, Simon J., primary, Bertoli, Cosetta, primary, Fenton, Tim R., primary, de Bruin, Robertus A.M., primary, Maya-Mendoza, Apolinar, primary, Santoni-Rugiu, Eric, primary, Hynds, Robert E., primary, Gorgoulis, Vassilis G., primary, Jamal-Hanjani, Mariam, primary, McGranahan, Nicholas, primary, Harris, Reuben S., primary, Janes, Sam M., primary, Bartkova, Jirina, primary, Bakhoum, Samuel F., primary, Bartek, Jiri, primary, Kanu, Nnennaya, primary, and Swanton, Charles, primary

Published
2023
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33. Non-Small-Cell Lung Cancer Promotion by Air Pollutants

Author

Swanton, Charles, primary, Hill, William, additional, Lim, Emilia, additional, Lee, Claudia, additional, Weeden, Clare, additional, Augustine, Marcellus, additional, Chen, Kezhong, additional, Kuan, Feng-Che, additional, Marongiu, Fabio, additional, Evans, Edward, additional, Moore, David, additional, Rodrigues, Felipe, additional, Maldegem, Febe van, additional, Boumelha, Jesse, additional, Veeriah, Selvaraju, additional, Rowan, Andrew, additional, Naceur-Lombardelli, Cristina, additional, Karasaki, Takahiro, additional, Sivakumar, Monica, additional, Caswell, Deborah, additional, Nagano, Ai, additional, Ryu, Min Hyung, additional, Huff, Ryan, additional, Li, Shijia, additional, Magness, Alastair, additional, Suarez-Bonnet, Alejandro, additional, Priestnall, Simon, additional, Lüchtenborg, Margreet, additional, Lavelle, Katrina, additional, Pethick, Joanna, additional, Hardy, Steven, additional, McRonald, Fiona, additional, Lin, Meng-Hung, additional, Troccoli, Clara, additional, Ghosh, Moumita, additional, Miller, York, additional, Merrick, Daniel, additional, Keith, Robert, additional, Bakir, Maise Al, additional, Bailey, Chris, additional, Saal, Lao, additional, Chen, Yilun, additional, George, Anthony, additional, Abbosh, Chris, additional, Kanu, Nnennaya, additional, Lee, Se-Hoon, additional, McGranahan, Nicholas, additional, Berg, Chistine, additional, Grönroos, Eva, additional, Downward, Julian, additional, Jacks, Tyler, additional, Carlsten, Christopher, additional, Malanchi, Ilaria, additional, Hackshaw, Allan, additional, Litchfield, Kevin, additional, Jamal-Hanjani, Mariam, additional, and DeGregori, James, additional

Published
2022
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34. CKS1 inhibition depletes leukemic stem cells and protects healthy hematopoietic stem cells in acute myeloid leukemia

Author

Grey, William, primary, Rio-Machin, Ana, additional, Casado, Pedro, additional, Grönroos, Eva, additional, Ali, Sara, additional, Miettinen, Juho J., additional, Bewicke-Copley, Findlay, additional, Parsons, Alun, additional, Heckman, Caroline A., additional, Swanton, Charles, additional, Cutillas, Pedro R., additional, Gribben, John, additional, Fitzgibbon, Jude, additional, and Bonnet, Dominique, additional

Published
2022
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35. Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, Angelova, Mihaela, Puttick, Clare, Zhai, Haoran, Caswell, Deborah R., Lu, Wei-ting, Dietzen, Michelle, Galanos, Panagiotis, Evangelou, Konstantinos, Bellelli, Roberto, Lim, Emilia L., Watkins, Thomas B.k., Rowan, Andrew, Teixeira, Vitor H., Zhao, Yue, Chen, Haiquan, Ngo, Bryan, Zalmas, Lykourgos-panagiotis, Al Bakir, Maise, Hobor, Sebastijan, Grönroos, Eva, Pennycuick, Adam, Nigro, Ersilia, Campbell, Brittany B., Brown, William L., Akarca, Ayse U., Marafioti, Teresa, Wu, Mary Y., Howell, Michael, Boulton, Simon J., Bertoli, Cosetta, Fenton, Tim R., De Bruin, Robertus A.m., Maya-mendoza, Apolinar, Santoni-rugiu, Eric, Hynds, Robert E., Gorgoulis, Vassilis G., Jamal-hanjani, Mariam, Mcgranahan, Nicholas, Harris, Reuben S., Janes, Sam M., Bartkova, Jirina, Bakhoum, Samuel F., Bartek, Jiri, Kanu, Nnennaya, Swanton, Charles, Venkatesan, Subramanian, Angelova, Mihaela, Puttick, Clare, Zhai, Haoran, Caswell, Deborah R., Lu, Wei-ting, Dietzen, Michelle, Galanos, Panagiotis, Evangelou, Konstantinos, Bellelli, Roberto, Lim, Emilia L., Watkins, Thomas B.k., Rowan, Andrew, Teixeira, Vitor H., Zhao, Yue, Chen, Haiquan, Ngo, Bryan, Zalmas, Lykourgos-panagiotis, Al Bakir, Maise, Hobor, Sebastijan, Grönroos, Eva, Pennycuick, Adam, Nigro, Ersilia, Campbell, Brittany B., Brown, William L., Akarca, Ayse U., Marafioti, Teresa, Wu, Mary Y., Howell, Michael, Boulton, Simon J., Bertoli, Cosetta, Fenton, Tim R., De Bruin, Robertus A.m., Maya-mendoza, Apolinar, Santoni-rugiu, Eric, Hynds, Robert E., Gorgoulis, Vassilis G., Jamal-hanjani, Mariam, Mcgranahan, Nicholas, Harris, Reuben S., Janes, Sam M., Bartkova, Jirina, Bakhoum, Samuel F., Bartek, Jiri, Kanu, Nnennaya, and Swanton, Charles

Abstract

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast ductal carcinoma in situ, and in preinvasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx preinvasive to invasive non–small cell lung cancer (NSCLC) lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early in cancer evolution. Significance: This study reveals the dynamics and drivers of APOBEC3 gene expression in preinvasive disease and the exacerbation of cellular diversity by APOBEC3B through DNA replication stress to promote chromosomal instability early in cancer evolution

Published
2021

36. LUNG CANCER EVOLUTION: Spatial and temporal diversity in genomic instability processes defines lung cancer evolution

Author

de Bruin, Elza C., McGranahan, Nicholas, Mitter, Richard, Salm, Max, Wedge, David C., Yates, Lucy, Jamal-Hanjani, Mariam, Shafi, Seema, Murugaesu, Nirupa, Rowan, Andrew J., Grönroos, Eva, Muhammad, Madiha A., Horswell, Stuart, Gerlinger, Marco, Varela, Ignacio, Jones, David, Marshall, John, Voet, Thierry, Van Loo, Peter, Rassl, Doris M., Rintoul, Robert C., Janes, Sam M., Lee, Siow-Ming, Forster, Martin, Ahmad, Tanya, Lawrence, David, Falzon, Mary, Capitanio, Arrigo, Harkins, Timothy T., Lee, Clarence C., Tom, Warren, Teefe, Enock, Chen, Shann-Ching, Begum, Sharmin, Rabinowitz, Adam, Phillimore, Benjamin, Spencer-Dene, Bradley, Stamp, Gordon, Szallasi, Zoltan, Matthews, Nik, Stewart, Aengus, Campbell, Peter, and Swanton, Charles

Published
2014
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37. Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

Author

Venkatesan, Subramanian, primary, Angelova, Mihaela, additional, Puttick, Clare, additional, Zhai, Haoran, additional, Caswell, Deborah R., additional, Lu, Wei-Ting, additional, Dietzen, Michelle, additional, Galanos, Panagiotis, additional, Evangelou, Konstantinos, additional, Bellelli, Roberto, additional, Lim, Emilia L., additional, Watkins, Thomas B.K., additional, Rowan, Andrew, additional, Teixeira, Vitor H., additional, Zhao, Yue, additional, Chen, Haiquan, additional, Ngo, Bryan, additional, Zalmas, Lykourgos-Panagiotis, additional, Al Bakir, Maise, additional, Hobor, Sebastijan, additional, Grönroos, Eva, additional, Pennycuick, Adam, additional, Nigro, Ersilia, additional, Campbell, Brittany B., additional, Brown, William L., additional, Akarca, Ayse U., additional, Marafioti, Teresa, additional, Wu, Mary Y., additional, Howell, Michael, additional, Boulton, Simon J., additional, Bertoli, Cosetta, additional, Fenton, Tim R., additional, de Bruin, Robertus A.M., additional, Maya-Mendoza, Apolinar, additional, Santoni-Rugiu, Eric, additional, Hynds, Robert E., additional, Gorgoulis, Vassilis G., additional, Jamal-Hanjani, Mariam, additional, McGranahan, Nicholas, additional, Harris, Reuben S., additional, Janes, Sam M., additional, Bartkova, Jirina, additional, Bakhoum, Samuel F., additional, Bartek, Jiri, additional, Kanu, Nnennaya, additional, and Swanton, Charles, additional

Published
2021
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41. Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal

Author

Turajlic, Samra, Xu, Hang, Litchfield, Kevin, Rowan, Andrew, Horswell, Stuart, Chambers, Tim, O'Brien, Tim, Lopez, Jose I, Watkins, Thomas BK, Nicol, David, Stares, Mark, Challacombe, Ben, Hazell, Steve, Chandra, Ashish, Mitchell, Thomas J, Au, Lewis, Eichler-Jonsson, Claudia, Jabbar, Faiz, Soultati, Aspasia, Chowdhury, Simon, Rudman, Sarah, Lynch, Joanna, Fernando, Archana, Stamp, Gordon, Nye, Emma, Stewart, Aengus, Xing, Wei, Smith, Jonathan C, Escudero, Mickael, Huffman, Adam, Matthews, Nik, Elgar, Greg, Phillimore, Ben, Costa, Marta, Begum, Sharmin, Ward, Sophia, Salm, Max, Boeing, Stefan, Fisher, Rosalie, Spain, Lavinia, Navas, Carolina, Grönroos, Eva, Hobor, Sebastijan, Sharma, Sarkhara, Aurangzeb, Ismaeel, Lall, Sharanpreet, Polson, Alexander, Varia, Mary, Horsfield, Catherine, Fotiadis, Nicos, Pickering, Lisa, Schwarz, Roland F, Silva, Bruno, Herrero, Javier, Luscombe, Nick M, Jamal-Hanjani, Mariam, Rosenthal, Rachel, Birkbak, Nicolai J, Wilson, Gareth A, Pipek, Orsolya, Ribli, Dezso, Krzystanek, Marcin, Csabai, Istvan, Szallasi, Zoltan, Gore, Martin, McGranahan, Nicholas, Van Loo, Peter, Campbell, Peter, Larkin, James, Swanton, Charles, TRACERx Renal Consortium, Mitchell, Thomas [0000-0003-0761-9503], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, intratumor heterogeneity, branched evolution, linear evolution, renal cell cancer, Chromosomes, Clonal Evolution, Evolution, Molecular, Genetic Heterogeneity, deterministic evolution, Biomarkers, Tumor, metastasis, Humans, Longitudinal Studies, Prospective Studies, Neoplasm Metastasis, Carcinoma, Renal Cell, Alleles, Phylogeny, Aged, Aged, 80 and over, cancer evolution, Models, Statistical, tumor diversity, Genetic Variation, punctuated evolution, Sequence Analysis, DNA, Middle Aged, Prognosis, Kidney Neoplasms, Phenotype, Mutation, Disease Progression, Female, chromosome instability
Abstract

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance.

Published
2018
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42. Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal

Author

Turajlic, Samra, primary, Xu, Hang, additional, Litchfield, Kevin, additional, Rowan, Andrew, additional, Horswell, Stuart, additional, Chambers, Tim, additional, O’Brien, Tim, additional, Lopez, Jose I., additional, Watkins, Thomas B.K., additional, Nicol, David, additional, Stares, Mark, additional, Challacombe, Ben, additional, Hazell, Steve, additional, Chandra, Ashish, additional, Mitchell, Thomas J., additional, Au, Lewis, additional, Eichler-Jonsson, Claudia, additional, Jabbar, Faiz, additional, Soultati, Aspasia, additional, Chowdhury, Simon, additional, Rudman, Sarah, additional, Lynch, Joanna, additional, Fernando, Archana, additional, Stamp, Gordon, additional, Nye, Emma, additional, Stewart, Aengus, additional, Xing, Wei, additional, Smith, Jonathan C., additional, Escudero, Mickael, additional, Huffman, Adam, additional, Matthews, Nik, additional, Elgar, Greg, additional, Phillimore, Ben, additional, Costa, Marta, additional, Begum, Sharmin, additional, Ward, Sophia, additional, Salm, Max, additional, Boeing, Stefan, additional, Fisher, Rosalie, additional, Spain, Lavinia, additional, Navas, Carolina, additional, Grönroos, Eva, additional, Hobor, Sebastijan, additional, Sharma, Sarkhara, additional, Aurangzeb, Ismaeel, additional, Lall, Sharanpreet, additional, Polson, Alexander, additional, Varia, Mary, additional, Horsfield, Catherine, additional, Fotiadis, Nicos, additional, Pickering, Lisa, additional, Schwarz, Roland F., additional, Silva, Bruno, additional, Herrero, Javier, additional, Luscombe, Nick M., additional, Jamal-Hanjani, Mariam, additional, Rosenthal, Rachel, additional, Birkbak, Nicolai J., additional, Wilson, Gareth A., additional, Pipek, Orsolya, additional, Ribli, Dezso, additional, Krzystanek, Marcin, additional, Csabai, Istvan, additional, Szallasi, Zoltan, additional, Gore, Martin, additional, McGranahan, Nicholas, additional, Van Loo, Peter, additional, Campbell, Peter, additional, Larkin, James, additional, and Swanton, Charles, additional

Published
2018
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43. Erratum: Corrigendum: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

Abbosh, Christopher, primary, Birkbak, Nicolai J., additional, Wilson, Gareth A., additional, Jamal-Hanjani, Mariam, additional, Constantin, Tudor, additional, Salari, Raheleh, additional, Le Quesne, John, additional, Moore, David A., additional, Veeriah, Selvaraju, additional, Rosenthal, Rachel, additional, Marafioti, Teresa, additional, Kirkizlar, Eser, additional, Watkins, Thomas B. K., additional, McGranahan, Nicholas, additional, Ward, Sophia, additional, Martinson, Luke, additional, Riley, Joan, additional, Fraioli, Francesco, additional, Al Bakir, Maise, additional, Grönroos, Eva, additional, Zambrana, Francisco, additional, Endozo, Raymondo, additional, Bi, Wenya Linda, additional, Fennessy, Fiona M., additional, Sponer, Nicole, additional, Johnson, Diana, additional, Laycock, Joanne, additional, Shafi, Seema, additional, Czyzewska-Khan, Justyna, additional, Rowan, Andrew, additional, Chambers, Tim, additional, Matthews, Nik, additional, Turajlic, Samra, additional, Hiley, Crispin, additional, Lee, Siow Ming, additional, Forster, Martin D., additional, Ahmad, Tanya, additional, Falzon, Mary, additional, Borg, Elaine, additional, Lawrence, David, additional, Hayward, Martin, additional, Kolvekar, Shyam, additional, Panagiotopoulos, Nikolaos, additional, Janes, Sam M., additional, Thakrar, Ricky, additional, Ahmed, Asia, additional, Blackhall, Fiona, additional, Summers, Yvonne, additional, Hafez, Dina, additional, Naik, Ashwini, additional, Ganguly, Apratim, additional, Kareht, Stephanie, additional, Shah, Rajesh, additional, Joseph, Leena, additional, Quinn, Anne Marie, additional, Crosbie, Phil A., additional, Naidu, Babu, additional, Middleton, Gary, additional, Langman, Gerald, additional, Trotter, Simon, additional, Nicolson, Marianne, additional, Remmen, Hardy, additional, Kerr, Keith, additional, Chetty, Mahendran, additional, Gomersall, Lesley, additional, Fennell, Dean A., additional, Nakas, Apostolos, additional, Rathinam, Sridhar, additional, Anand, Girija, additional, Khan, Sajid, additional, Russell, Peter, additional, Ezhil, Veni, additional, Ismail, Babikir, additional, Irvin-Sellers, Melanie, additional, Prakash, Vineet, additional, Lester, Jason F., additional, Kornaszewska, Malgorzata, additional, Attanoos, Richard, additional, Adams, Haydn, additional, Davies, Helen, additional, Oukrif, Dahmane, additional, Akarca, Ayse U., additional, Hartley, John A., additional, Lowe, Helen L., additional, Lock, Sara, additional, Iles, Natasha, additional, Bell, Harriet, additional, Ngai, Yenting, additional, Elgar, Greg, additional, Szallasi, Zoltan, additional, Schwarz, Roland F., additional, Herrero, Javier, additional, Stewart, Aengus, additional, Quezada, Sergio A., additional, Peggs, Karl S., additional, Van Loo, Peter, additional, Dive, Caroline, additional, Lin, C. Jimmy, additional, Rabinowitz, Matthew, additional, Aerts, Hugo J. W. L., additional, Hackshaw, Allan, additional, Shaw, Jacqui A., additional, Zimmermann, Bernhard G., additional, and Swanton, Charles, additional

Published
2017
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44. BCL9L Dysfunction Impairs Caspase-2 Expression Permitting Aneuploidy Tolerance in Colorectal Cancer

Author

López-García, Carlos, primary, Sansregret, Laurent, additional, Domingo, Enric, additional, McGranahan, Nicholas, additional, Hobor, Sebastijan, additional, Birkbak, Nicolai Juul, additional, Horswell, Stuart, additional, Grönroos, Eva, additional, Favero, Francesco, additional, Rowan, Andrew J., additional, Matthews, Nicholas, additional, Begum, Sharmin, additional, Phillimore, Benjamin, additional, Burrell, Rebecca, additional, Oukrif, Dahmane, additional, Spencer-Dene, Bradley, additional, Kovac, Michal, additional, Stamp, Gordon, additional, Stewart, Aengus, additional, Danielsen, Havard, additional, Novelli, Marco, additional, Tomlinson, Ian, additional, and Swanton, Charles, additional

Published
2017
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45. BCL9L Dysfunction Impairs Caspase-2 Expression Permitting Aneuploidy Tolerance in Colorectal Cancer

Author

López-García, Carlos, Sansregret, Laurent, Domingo, Enric, McGranahan, Nicholas, Hobor, Sebastijan, Birkbak, Nicolai Juul, Horswell, Stuart, Grönroos, Eva, Favero, Francesco, Rowan, Andrew J., Matthews, Nicholas, Begum, Sharmin, Phillimore, Benjamin, Burrell, Rebecca, Oukrif, Dahmane, Spencer-Dene, Bradley, Kovac, Michal, Stamp, Gordon, Stewart, Aengus, Danielsen, Havard, Novelli, Marco, Tomlinson, Ian, Swanton, Charles, López-García, Carlos, Sansregret, Laurent, Domingo, Enric, McGranahan, Nicholas, Hobor, Sebastijan, Birkbak, Nicolai Juul, Horswell, Stuart, Grönroos, Eva, Favero, Francesco, Rowan, Andrew J., Matthews, Nicholas, Begum, Sharmin, Phillimore, Benjamin, Burrell, Rebecca, Oukrif, Dahmane, Spencer-Dene, Bradley, Kovac, Michal, Stamp, Gordon, Stewart, Aengus, Danielsen, Havard, Novelli, Marco, Tomlinson, Ian, and Swanton, Charles

Abstract

Chromosomal instability (CIN) contributes to cancer evolution, intratumor heterogeneity, and drug resistance. CIN is driven by chromosome segregation errors and a tolerance phenotype that permits the propagation of aneuploid genomes. Through genomic analysis of colorectal cancers and cell lines, we find frequent loss of heterozygosity and mutations in BCL9L in aneuploid tumors. BCL9L deficiency promoted tolerance of chromosome missegregation events, propagation of aneuploidy, and genetic heterogeneity in xenograft models likely through modulation of Wnt signaling. We find that BCL9L dysfunction contributes to aneuploidy tolerance in both TP53-WT and mutant cells by reducing basal caspase-2 levels and preventing cleavage of MDM2 and BID. Efforts to exploit aneuploidy tolerance mechanisms and the BCL9L/caspase-2/BID axis may limit cancer diversity and evolution.

Published
2016

46. Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

Author

Fisher, Rosalie, Horswell, Stuart, Rowan, Andrew, Salm, Maximilian P., de Bruin, Elza C., Gulati, Sakshi, McGranahan, Nicholas, Stares, Mark, Gerlinger, Marco, Varela, Ignacio, Crockford, Andrew, Favero, Francesco, Quidville, Virginie, André, Fabrice, Navas, Carolina, Grönroos, Eva, Nicol, David, Hazell, Steve, Hrouda, David, O’Brien, Tim, Matthews, Nik, Phillimore, Ben, Begum, Sharmin, Rabinowitz, Adam, Biggs, Jennifer, Bates, Paul A., McDonald, Neil Q., Stamp, Gordon, Spencer-Dene, Bradley, Hsieh, James J., Xu, Jianing, Pickering, Lisa, Gore, Martin, Larkin, James, Swanton, Charles, Fisher, Rosalie, Horswell, Stuart, Rowan, Andrew, Salm, Maximilian P., de Bruin, Elza C., Gulati, Sakshi, McGranahan, Nicholas, Stares, Mark, Gerlinger, Marco, Varela, Ignacio, Crockford, Andrew, Favero, Francesco, Quidville, Virginie, André, Fabrice, Navas, Carolina, Grönroos, Eva, Nicol, David, Hazell, Steve, Hrouda, David, O’Brien, Tim, Matthews, Nik, Phillimore, Ben, Begum, Sharmin, Rabinowitz, Adam, Biggs, Jennifer, Bates, Paul A., McDonald, Neil Q., Stamp, Gordon, Spencer-Dene, Bradley, Hsieh, James J., Xu, Jianing, Pickering, Lisa, Gore, Martin, Larkin, James, and Swanton, Charles

Abstract

Background : Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution. Results : We perform whole exome sequencing on four clear cell renal cell carcinomas removed from both kidneys of a patient with a germline VHL mutation. We report that tumors arising in this context are clonally independent and harbour distinct secondary events exemplified by loss of chromosome 3p, despite an identical genetic background and tissue microenvironment. We propose that divergent mutational and copy number anomalies are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient, and in a second, older patient with VHL syndrome demonstrate minimal intra-tumor heterogeneity and mutational burden, and evaluable tumors appear to follow a linear evolutionary route, compared to tumors from patients with sporadic clear cell renal cell carcinoma. Conclusions : In tumors developing from a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity.

Published
2014

47. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

Author

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, and Grönroos, Eva

Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2017
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48. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution

Author

de Bruin, Elza C., primary, McGranahan, Nicholas, additional, Mitter, Richard, additional, Salm, Max, additional, Wedge, David C., additional, Yates, Lucy, additional, Jamal-Hanjani, Mariam, additional, Shafi, Seema, additional, Murugaesu, Nirupa, additional, Rowan, Andrew J., additional, Grönroos, Eva, additional, Muhammad, Madiha A., additional, Horswell, Stuart, additional, Gerlinger, Marco, additional, Varela, Ignacio, additional, Jones, David, additional, Marshall, John, additional, Voet, Thierry, additional, Van Loo, Peter, additional, Rassl, Doris M., additional, Rintoul, Robert C., additional, Janes, Sam M., additional, Lee, Siow-Ming, additional, Forster, Martin, additional, Ahmad, Tanya, additional, Lawrence, David, additional, Falzon, Mary, additional, Capitanio, Arrigo, additional, Harkins, Timothy T., additional, Lee, Clarence C., additional, Tom, Warren, additional, Teefe, Enock, additional, Chen, Shann-Ching, additional, Begum, Sharmin, additional, Rabinowitz, Adam, additional, Phillimore, Benjamin, additional, Spencer-Dene, Bradley, additional, Stamp, Gordon, additional, Szallasi, Zoltan, additional, Matthews, Nik, additional, Stewart, Aengus, additional, Campbell, Peter, additional, and Swanton, Charles, additional

Published
2014
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49. Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

Author

Fisher, Rosalie, primary, Horswell, Stuart, additional, Rowan, Andrew, additional, Salm, Maximilian P, additional, de Bruin, Elza C, additional, Gulati, Sakshi, additional, McGranahan, Nicholas, additional, Stares, Mark, additional, Gerlinger, Marco, additional, Varela, Ignacio, additional, Crockford, Andrew, additional, Favero, Francesco, additional, Quidville, Virginie, additional, André, Fabrice, additional, Navas, Carolina, additional, Grönroos, Eva, additional, Nicol, David, additional, Hazell, Steve, additional, Hrouda, David, additional, O’Brien, Tim, additional, Matthews, Nik, additional, Phillimore, Ben, additional, Begum, Sharmin, additional, Rabinowitz, Adam, additional, Biggs, Jennifer, additional, Bates, Paul A, additional, McDonald, Neil Q, additional, Stamp, Gordon, additional, Spencer-Dene, Bradley, additional, Hsieh, James J, additional, Xu, Jianing, additional, Pickering, Lisa, additional, Gore, Martin, additional, Larkin, James, additional, and Swanton, Charles, additional

Published
2014
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50. Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Author

Dewhurst, Sally M., primary, McGranahan, Nicholas, additional, Burrell, Rebecca A., additional, Rowan, Andrew J., additional, Grönroos, Eva, additional, Endesfelder, David, additional, Joshi, Tejal, additional, Mouradov, Dmitri, additional, Gibbs, Peter, additional, Ward, Robyn L., additional, Hawkins, Nicholas J., additional, Szallasi, Zoltan, additional, Sieber, Oliver M., additional, and Swanton, Charles, additional

Published
2014
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