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3. 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

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

Author

Al Bakir, Maise, Huebner, Ariana, Martínez-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 M., 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 A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J., Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2023
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8. Genomic–transcriptomic evolution in lung cancer and metastasis

Author

Martínez-Ruiz, Carlos, Black, James R. M., Puttick, Clare, Hill, Mark S., Demeulemeester, Jonas, Larose Cadieux, Elizabeth, Thol, Kerstin, Jones, Thomas P., Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Prymas, Paulina, Rowan, Andrew, Ward, Sophia, Cubitt, Laura, Athanasopoulou, Foteini, Pich, Oriol, Karasaki, Takahiro, Moore, David A., Salgado, Roberto, Colliver, Emma, Castignani, Carla, Dietzen, Michelle, Huebner, Ariana, Al Bakir, Maise, Tanić, Miljana, Watkins, Thomas B. K., Lim, Emilia L., Al-Rashed, Ali M., Lang, Danny, Clements, James, Cook, Daniel E., Rosenthal, Rachel, Wilson, Gareth A., Frankell, Alexander M., de Carné Trécesson, Sophie, East, Philip, Kanu, Nnennaya, Litchfield, Kevin, Birkbak, Nicolai J., Hackshaw, Allan, Beck, Stephan, Van Loo, Peter, Jamal-Hanjani, Mariam, Swanton, Charles, and McGranahan, Nicholas

Published
2023
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9. 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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10. 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

11. Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study

Author

Fu, Xiao, Zhao, Yue, Lopez, Jose I., Rowan, Andrew, Au, Lewis, Fendler, Annika, Hazell, Steve, Xu, Hang, Horswell, Stuart, Shepherd, Scott T. C., Spencer, Charlotte E., Spain, Lavinia, Byrne, Fiona, Stamp, Gordon, O’Brien, Tim, Nicol, David, Augustine, Marcellus, Chandra, Ashish, Rudman, Sarah, Toncheva, Antonia, Furness, Andrew J. S., Pickering, Lisa, Kumar, Santosh, Koh, Dow-Mu, Messiou, Christina, Dafydd, Derfel ap, Orton, Matthew R., Doran, Simon J., Larkin, James, Swanton, Charles, Sahai, Erik, Litchfield, Kevin, Turajlic, Samra, and Bates, Paul A.

Published
2022
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13. Using DNA sequencing data to quantify T cell fraction and therapy response

Author

Bentham, Robert, Litchfield, Kevin, Watkins, Thomas B. K., Lim, Emilia L., Rosenthal, Rachel, Martínez-Ruiz, Carlos, Hiley, Crispin T., Bakir, Maise Al, Salgado, Roberto, Moore, David A., Jamal-Hanjani, Mariam, Birkbak, Nicolai J., Escudero, Mickael, Stewart, Aengus, Rowan, Andrew, and Goldman, Jacki

Subjects
Nucleotide sequencing -- Methods, T cells -- Physiological aspects -- Genetic aspects, Cellular therapy -- Methods, DNA sequencing -- Methods, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy.sup.1,2. However, measurements of tumour infiltrating lymphocytes (TILs) are limited by a shortage of appropriate data. Whole-exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations. Here we develop T cell exome TREC tool (T cell ExTRECT), a method for estimation of T cell fraction from WES samples using a signal from T cell receptor excision circle (TREC) loss during V(D)J recombination of the T cell receptor-[alpha] gene (TCRA (also known as TRA)). TCRA T cell fraction correlates with orthogonal TIL estimates and is agnostic to sample type. Blood TCRA T cell fraction is higher in females than in males and correlates with both tumour immune infiltrate and presence of bacterial sequencing reads. Tumour TCRA T cell fraction is prognostic in lung adenocarcinoma. Using a meta-analysis of tumours treated with immunotherapy, we show that tumour TCRA T cell fraction predicts immunotherapy response, providing value beyond measuring tumour mutational burden. Applying T cell ExTRECT to a multi-sample pan-cancer cohort reveals a high diversity of the degree of immune infiltration within tumours. Subclonal loss of 12q24.31-32, encompassing SPPL3, is associated with reduced TCRA T cell fraction. T cell ExTRECT provides a cost-effective technique to characterize immune infiltrate alongside somatic changes. A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy., Author(s): Robert Bentham [sup.1] [sup.2] , Kevin Litchfield [sup.2] [sup.3] , Thomas B. K. Watkins [sup.4] , Emilia L. Lim [sup.2] [sup.4] , Rachel Rosenthal [sup.4] , Carlos Martínez-Ruiz [sup.1] [...]

Published
2021
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14. Clinical outcomes of COVID-19 in long-term care facilities for people with epilepsy

Author

Aitken, Jim, Allen, Zoe, Ambler, Rachel, Ambrose, Karen, Ashton, Emma, Avola, Alida, Balakrishnan, Samutheswari, Barns-Jenkins, Caitlin, Barr, Genevieve, Barrell, Sam, Basu, Souradeep, Beale, Rupert, Beesley, Clare, Bhardwaj, Nisha, Bibi, Shahnaz, Bineva-Todd, Ganka, Biswas, Dhruva, Blackman, Michael J., Bonnet, Dominique, Bowker, Faye, Broncel, Malgorzata, Brooks, Claire, Buck, Michael D., Buckton, Andrew, Budd, Timothy, Burrell, Alana, Busby, Louise, Bussi, Claudio, Butterworth, Simon, Byott, Matthew, Byrne, Fiona, Byrne, Richard, Caidan, Simon, Campbell, Joanna, Canton, Johnathan, Cardoso, Ana, Carter, Nick, Carvalho, Luiz, Carzaniga, Raffaella, Chandler, Natalie, Chen, Qu, Cherepanov, Peter, Churchward, Laura, Clark, Graham, Clayton, Bobbi, Cobolli Gigli, Clementina, Collins, Zena, Cottrell, Sally, Crawford, Margaret, Cubitt, Laura, Cullup, Tom, Davies, Heledd, Davis, Patrick, Davison, Dara, Dearing, Vicky, Debaisieux, Solene, Diaz-Romero, Monica, Dibbs, Alison, Diring, Jessica, Driscoll, Paul C., D'Avola, Annalisa, Earl, Christopher, Edwards, Amelia, Ekin, Chris, Evangelopoulos, Dimitrios, Faraway, Rupert, Fearns, Antony, Ferron, Aaron, Fidanis, Efthymios, Fitz, Dan, Fleming, James, Frampton, Daniel, Frederico, Bruno, Gaiba, Alessandra, Gait, Anthony, Gamblin, Steve, Gärtner, Kathleen, Gaul, Liam, Golding, Helen M., Goldman, Jacki, Goldstone, Robert, Gomez Dominguez, Belen, Gong, Hui, Grant, Paul R., Greco, Maria, Grobler, Mariana, Guedan, Anabel, Gutierrez, Maximiliano G., Hackett, Fiona, Hall, Ross, Halldorsson, Steinar, Harris, Suzanne, Hashim, Sugera, Hatipoglu, Emine, Healy, Lyn, Heaney, Judith, Herbst, Susanne, Hewitt, Graeme, Higgins, Theresa, Hindmarsh, Steve, Hirani, Rajnika, Hope, Joshua, Horton, Elizabeth, Hoskins, Beth, Howell, Michael, Howitt, Louise, Hoyle, Jacqueline, Htun, Mint R., Hubank, Michael, Huerga Encabo, Hector, Hughes, Deborah, Hughes, Jane, Huseynova, Almaz, Hwang, Ming-Shih, Instrell, Rachael, Jackson, Deborah, Jamal-Hanjani, Mariam, Jenkins, Lucy, Jiang, Ming, Johnson, Mark, Jones, Leigh, Kanu, Nnennaya, Kassiotis, George, Kelly, Gavin, Kiely, Louise, Teixeira, Anastacio King Spert, Kirk, Stuart, Kjaer, Svend, Knuepfer, Ellen, Komarov, Nikita, Kotzampaltiris, Paul, Kousis, Konstantinos, Krylova, Tammy, Kucharska, Ania, Labrum, Robyn, Lambe, Catherine, Lappin, Michelle, Lee, Stacey-Ann, Levett, Andrew, Levett, Lisa, Levi, Marcel, Liu, Hon Wing, Loughlin, Sam, Lu, Wei-Ting, MacRae, James I., Madoo, Akshay, Marczak, Julie A., Martensson, Mimmi, Martinez, Thomas, Marzook, Bishara, Matthews, John, Matz, Joachim M., McCall, Samuel, McCoy, Laura E., McKay, Fiona, McNamara, Edel C., Minutti, Carlos M., Mistry, Gita, Molina-Arcas, Miriam, Montaner, Beatriz, Montgomery, Kylie, Moore, Catherine, Moore, David, Moraiti, Anastasia, Moreira-Teixeira, Lucia, Mukherjee, Joyita, Naceur-Lombardelli, Cristina, Nelson, Aileen, Nicod, Jerome, Nightingale, Luke, Nofal, Stephanie, Nurse, Paul, Nutan, Savita, Oedekoven, Caroline, O'Garra, Anne, O'Leary, Jean D., Olsen, Jessica, O'Neill, Olga, O'Reilly, Nicola, Suarez, Paula Ordonez, Osborne, Neil, Pabari, Amar, Pajak, Aleksandra, Papayannopoulos, Venizelos, Paraskevopoulou, Stavroula M, Patel, Namita, Patel, Yogen, Paun, Oana, Peat, Nigel, Peces-Barba Castano, Laura, Caballero, Ana Perez, Perez-Lloret, Jimena, Perrault, Magali S., Perrin, Abigail, Poh, Roy, Poirier, Enzo Z., Polke, James M., Pollitt, Marc, Prieto-Godino, Lucia, Proust, Alize, Puvirajasinghe, Clinda, Queval, Christophe, Ramachandran, Vijaya, Ramaprasad, Abhinay, Ratcliffe, Peter, Reed, Laura, Reis e Sousa, Caetano, Richardson, Kayleigh, Ridewood, Sophie, Roberts, Fiona, Roberts, Rowenna, Rodgers, Angela, Romero Clavijo, Pablo, Rosa, Annachiara, Rossi, Alice, Roustan, Chloe, Rowan, Andrew, Sahai, Erik, Sait, Aaron, Sala, Katarzyna, Sanchez, Emilie, Sanderson, Theo, Santucci, Pierre, Sardar, Fatima, Sateriale, Adam, Saunders, Jill A., Sawyer, Chelsea, Schlott, Anja, Schweighoffer, Edina, Segura-Bayona, Sandra, Shah Punatar, Rajvee, Shahmanesh, Maryam, Shaw, Joe, Silva Dos Santos, Mariana, Silvestre, Margaux, Singer, Matthew, Snell, Daniel M., Song, Ok-Ryul, Spyer, Moira J., Steel, Louisa, Strange, Amy, Sullivan, Adrienne E., Tan, Michele S.Y., Tautz-Davis, Zoe H., Taylor, Effie, Taylor, Gunes, Taylor, Harriet B., Taylor-Beadling, Alison, Teixeira Subtil, Fernanda, Terré Torras, Berta, Toolan-Kerr, Patrick, Torelli, Francesca, Toteva, Tea, Treeck, Moritz, Trojer, Hadija, Tsai, Ming-Han C., Turner, James M.A., Turner, Melanie, Ule, Jernej, Ulferts, Rachel, Vanloo, Sharon P., Veeriah, Selvaraju, Venkatesan, Subramanian, Vousden, Karen, Wack, Andreas, Walder, Claire, Walker, Philip A., Wang, Yiran, Ward, Sophia, Wenman, Catharina, Williams, Luke, Williams, Matthew J., Keong Wong, Wai, Wright, Joshua, Wu, Mary, Wynne, Lauren, Xiang, Zheng, Yap, Melvyn, Zagalak, Julian A., Zecchin, Davide, Zillwood, Rachel, Carthiyaniamma, Santhakumari, DeTisi, Jane, Dick, Julie, Hill, Andrea, Kipper, Karin, Kullar, Birinder, Norris, Sarah, Rugg-Gunn, Fergus, Salvatierra, Rebecca, Shaya, Gabriel, Sloan, Astrid, Singh, Priyanka, Varley, James, Whatley, Ben, Balestrini, Simona, Koepp, Matthias J., Gandhi, Sonia, Rickman, Hannah M., Shin, Gee Yen, Houlihan, Catherine F., Anders-Cannon, Jonny, Silvennoinen, Katri, Xiao, Fenglai, Zagaglia, Sara, Hudgell, Kirsty, Ziomek, Mariusz, Haimes, Paul, Sampson, Adam, Parker, Annie, Helen Cross, J., Pardington, Rosemarie, Nastouli, Eleni, Swanton, Charles, Sander, Josemir W., and Sisodiya, Sanjay M.

Published
2021
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15. Matriptase Induction of Metalloproteinase‐Dependent Aggrecanolysis In Vitro and In Vivo: Promotion of Osteoarthritic Cartilage Damage by Multiple Mechanisms

Author

Wilkinson, David J, Wang, Hui, Habgood, Angela, Lamb, Heather K, Thompson, Paul, Hawkins, Alastair R, Désilets, Antoine, Leduc, Richard, Steinmetzer, Torsten, Hammami, Maya, Lee, Melody S, Craik, Charles S, Watson, Sharon, Lin, Hua, Milner, Jennifer M, and Rowan, Andrew D

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Arthritis, Aging, Osteoarthritis, Biotechnology, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, Aetiology, 5.1 Pharmaceuticals, Musculoskeletal, ADAMTS4 Protein, ADAMTS5 Protein, Aged, Aged, 80 and over, Aggrecans, Animals, Antibodies, Neutralizing, Blotting, Western, Cartilage, Articular, Endopeptidases, Female, Gene Expression Profiling, Humans, Immunohistochemistry, In Vitro Techniques, Low Density Lipoprotein Receptor-Related Protein-1, Male, Matrix Metalloproteinases, Membrane Proteins, Menisci, Tibial, Mice, Middle Aged, Osteoarthritis, Knee, Real-Time Polymerase Chain Reaction, Recombinant Proteins, Serine Endopeptidases, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveTo assess the ability of matriptase, a type II transmembrane serine proteinase, to promote aggrecan loss from the cartilage of patients with osteoarthritis (OA) and to determine whether its inhibition can prevent aggrecan loss and cartilage damage in experimental OA.MethodsAggrecan release from human OA cartilage explants and human stem cell-derived cartilage discs was evaluated, and cartilage-conditioned media were used for Western blotting. Gene expression was analyzed by real-time polymerase chain reaction. Murine OA was induced by surgical destabilization of the medial meniscus, and matriptase inhibitors were administered via osmotic minipump or intraarticular injection. Cartilage damage was scored histologically and aggrecan cleavage was visualized immunohistochemically using specific neoepitope antibodies.ResultsThe addition of soluble recombinant matriptase promoted a time-dependent release of aggrecan (and collagen) from OA cartilage, which was sensitive to metalloproteinase inhibition and protease-activated receptor 2 antagonism. Although engineered human (normal) cartilage discs failed to release aggrecan following matriptase addition, both matrix metalloproteinase- and aggrecanase-mediated cleavages of aggrecan were detected in human OA cartilage. Additionally, while matriptase did not directly degrade aggrecan, it promoted the accumulation of low-density lipoprotein receptor-related protein 1 (LRP-1) in conditioned media of the OA cartilage explants. Matriptase inhibition via neutralizing antibody or small molecule inhibitor significantly reduced cartilage damage scores in murine OA, which was associated with reduced generation of metalloproteinase-mediated aggrecan cleavage.ConclusionMatriptase potently induces the release of metalloproteinase-generated aggrecan fragments as well as soluble LRP-1 from OA cartilage. Therapeutic targeting of matriptase proteolytic activity reduces metalloproteinase activity, further suggesting that this serine proteinase may have potential as a disease-modifying therapy in OA.

Published
2017

16. Application of rational enzyme engineering in a new route to etonogestrel and levonorgestrel: carbonyl reductase bioreduction of ethyl secodione.

Author

Dourado, Daniel F. A. R., Rowan, Andrew S., Maciuk, Sergej, Brown, Gareth, Gray, Darren, Spratt, Jenny, Carvalho, Alexandra T. P., Pavlović, Draηen, Tur, Fernando, Caswell, Jill, Quinn, Derek J., Moody, Thomas S., and Mix, Stefan

Abstract

Women in developing countries still face enormous challenges when accessing reproductive health care. Access to voluntary family planning empowers women allowing them to complete their education and join the paid workforce. This effectively helps to end poverty, hunger and promotes good health for all. According to the United Nations (UN) organization, in 2022, an estimated 257 million women still lacked access to safe and effective family planning methods globally. One of the main barriers is the associated cost of modern contraceptive methods. Funded by the Bill & Melinda Gates Foundation, Almac Group worked on the development of a novel biocatalytic route to etonogestrel and levonorgestrel, two modern contraceptive APIs, with the goal of substantially decreasing the cost of production and so enabling their use in developing nations. This present work combines the selection and engineering of a carbonyl reductase (CRED) enzyme from Almac's selectAZyme™ panel, with process development, to enable efficient and economically viable bioreduction of ethyl secodione to (13R,17S)-secol, the key chirality introducing intermediate en route to etonogestrel and levonorgestrel API. CRED library screening returned a good hit with an Almac CRED from Bacillus weidmannii, which allowed for highly stereoselective bioreduction at low enzyme loading of less than 1% w/w under screening assay conditions. However, the only co-solvent tolerated was DMSO up to ∼30% v/v, and it was impossible to achieve reaction completion with any enzyme loading at substrate titres of 20 g L−1 and above, due to the insolubility of the secodione. This triggered a rapid enzyme engineering program fully based on computational mutant selection. A small panel of 93 CRED mutants was rationally designed to increase the catalytic activity as well as thermal and solvent stability. The best mutant, Mutant-75, enabled a reaction at 45 °C to go to completion at 90 g L−1 substrate titre in a buffer/DMSO/heptane reaction medium fed over 6 h with substrate DMSO stock solution, with a low enzyme loading of 3.5% w/w wrt substrate. In screening assay conditions, Mutant-75 also showed a 2.2-fold activity increase. Our paper shows which computations and rational decisions enabled this outcome. [ABSTRACT FROM AUTHOR]

Published
2024
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18. 60 Years of the 3Rs Symposium: Lessons Learned and the Road Ahead.

Author

Balls, Michael, Bass, Rolf, Curren, Rodger, Fentem, Julia, Goldberg, Alan, Hartung, Thomas, Herrmann, Kathrin, Kleinstreuer, Nicole C., Libowitz, Lisa, Parascandola, John, Rowan, Andrew N., Spielmann, Horst, Stephens, Martin L., Thomas, Russell S., and Tsaioun, Katya

Abstract

When The Principles of Humane Experimental Technique was published in 1959, authors William Russell and Rex Burch had a modest goal: to make researchers think about what they were doing in the laboratory -- and to do it more humanely. Sixty years later, their groundbreaking book was celebrated for inspiring a revolution in science and launching a new field: The 3Rs of alternatives to animal experimentation. On November 22, 2019, some pioneering and leading scientists and researchers in the field gathered at the Johns Hopkins Bloomberg School of Public Health in Baltimore for the 60 Years of the 3Rs Symposium: Lessons Learned and the Road Ahead. The event was sponsored by the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), the Foundation for Chemistry Research and Initiatives, the Alternative Research & Development Foundation (ARDF), the American Cleaning Institute (ACI), the International Fragrance Association (IFRA), the Institute for In Vitro Sciences (IIVS), John "Jack" R. Fowle III, and the Society of Toxicology (SoT). Fourteen presentations shared the history behind the groundbreaking publication, international efforts to achieve its aims, stumbling blocks to progress, as well as remarkable achievements. The day was a tribute to Russell and Burch, and a testament to what is possible when people from many walks of life -- science, government, and industry -- work toward a common goal. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Silencing of a BAHD acyltransferase in sugarcane increases biomass digestibility

Author

Wagner Rodrigo de Souza, Thályta Fraga Pacheco, Karoline Estefani Duarte, Bruno Leite Sampaio, Patrícia Abrão de Oliveira Molinari, Polyana Kelly Martins, Thaís Ribeiro Santiago, Eduardo Fernandes Formighieri, Felipe Vinecky, Ana Paula Ribeiro, Bárbara Andrade Dias Brito da Cunha, Adilson Kenji Kobayashi, Rowan Andrew Craig Mitchell, Dasciana de Sousa Rodrigues Gambetta, and Hugo Bruno Correa Molinari

Subjects
Sugarcane, Cell-wall acylation, Biomass, Lignocellulosic feedstock, Biofuels, Fuel, TP315-360, Biotechnology, TP248.13-248.65
Abstract

Abstract Background Sugarcane (Saccharum spp.) covers vast areas of land (around 25 million ha worldwide), and its processing is already linked into infrastructure for producing bioethanol in many countries. This makes it an ideal candidate for improving composition of its residues (mostly cell walls), making them more suitable for cellulosic ethanol production. In this paper, we report an approach to improving saccharification of sugarcane straw by RNAi silencing of the recently discovered BAHD01 gene responsible for feruloylation of grass cell walls. Results We identified six BAHD genes in the sugarcane genome (SacBAHDs) and generated five lines with substantially decreased SacBAHD01 expression. To find optimal conditions for determining saccharification of sugarcane straw, we tried multiple combinations of solvent and temperature pretreatment conditions, devising a predictive model for finding their effects on glucose release. Under optimal conditions, demonstrated by Organosolv pretreatment using 30% ethanol for 240 min, transgenic lines showed increases in saccharification efficiency of up to 24%. The three lines with improved saccharification efficiency had lower cell-wall ferulate content but unchanged monosaccharide and lignin compositions. Conclusions The silencing of SacBAHD01 gene and subsequent decrease of cell-wall ferulate contents indicate a promising novel biotechnological approach for improving the suitability of sugarcane residues for cellulosic ethanol production. In addition, the Organosolv pretreatment of the genetically modified biomass and the optimal conditions for the enzymatic hydrolysis presented here might be incorporated in the sugarcane industry for bioethanol production.

Published
2019
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20. Outdoor Cats: An Animal Welfare and Protection Perspective

Author

Hadidian, John, Gibson, Inga, Hagood, Susan, Peterson, Nancy, Unti, Bernie, McFarland, Betsy, Lisnik, Katie, Bialy, Heather, Fricke, Inga, Schatzmann, Kathleen, Fearing, Jennifer, Runquist, Pam, and Rowan, Andrew

Subjects
birds, cats, feral cats, Hawaii, preferred management approaches, San Nicolas Island, TNR, trap-neuter-return, wildlife
Abstract

First raised as a serious conservation issue more than 100 years ago, the impact of free-roaming cats on wildlife has been a subject of debate, controversy, and conflict since then. Cats have been tied directly to the extinction of sensitive species in island environments and implicated as major threats to certain wildlife populations elsewhere. Yet the study of free-roaming cats and the problems attributed to them lags behind the standards of research typical with more traditional vertebrate “pest” species. Alternative management approaches, ranging from traditional practices such as removal and depopulation to emerging concepts such as Trap-Neuter-Return (TNR), have yet to be subject to the scrutiny and experimental study that could lay controversial interpretations of their efficacy to rest. Here, we discuss the need for collaborative management concepts and programs to address growing concerns about cats outdoors.

Published
2012

21. A 'click chemistry' approach to the synthetics of nucleoside triphosphate mimetics

Author

Rowan, Andrew Stephen

Subjects
572.8
Abstract

Nucleoside triphosphates (NTPs) are substrates for numerous NTP-dependent enzymes within the body, and thus are crucial for a wide variety of biological processes. NTP mimetics would therefore be ideal candidates for chemical genetics programmes, to perturb intracellular processes with exquisite precision by the inhibition of selected proteins. We believe that replacement of the ~,y-pyrophosphate moiety of an NTP with a monosaccharide may still lead to favourable enzyme binding but lead to inhibition. Replacement of the a-phosphate group with a triazole linker would facilitate cell permeability by removing any remaining charge, as well as increase stability of the mimetic. Triazoles can be formed via the Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition reaction of azides and terminal alkynes. A series of propargyl glycosides of various monosaccharides have been synthesised, in most cases possessing anomeric purity, and reliable protocols developed. A number of 5'azido nucleosides have also been synthesised, and coupling reactions carried out to obtain a library of 45 novel sugar-triazole-nucleosides. These compounds have been tested as potential inhibitors of the type III pantothenate kinase from Bacillus anthracis and one potent inhibitor discovered with a Kj of 164 p.M. This shows that the inhibitor binds approximately three times more tightly in the active site than the natural substrate ATP (Km = 475 M).

Published
2008

23. Data from Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

Author

Spain, Lavinia, primary, Coulton, Alexander, primary, Lobon, Irene, primary, Rowan, Andrew, primary, Schnidrig, Desiree, primary, Shepherd, Scott T.C., primary, Shum, Benjamin, primary, Byrne, Fiona, primary, Goicoechea, Maria, primary, Piperni, Elisa, primary, Au, Lewis, primary, Edmonds, Kim, primary, Carlyle, Eleanor, primary, Hunter, Nikki, primary, Renn, Alexandra, primary, Messiou, Christina, primary, Hughes, Peta, primary, Nobbs, Jaime, primary, Foijer, Floris, primary, van den Bos, Hilda, primary, Wardenaar, Rene, primary, Spierings, Diana C.J., primary, Spencer, Charlotte, primary, Schmitt, Andreas M., primary, Tippu, Zayd, primary, Lingard, Karla, primary, Grostate, Lauren, primary, Peat, Kema, primary, Kelly, Kayleigh, primary, Sarker, Sarah, primary, Vaughan, Sarah, primary, Mangwende, Mary, primary, Terry, Lauren, primary, Kelly, Denise, primary, Biano, Jennifer, primary, Murra, Aida, primary, Korteweg, Justine, primary, Lewis, Charlotte, primary, O'Flaherty, Molly, primary, Cattin, Anne-Laure, primary, Emmerich, Max, primary, Gerard, Camille L., primary, Pallikonda, Husayn Ahmed, primary, Lynch, Joanna, primary, Mason, Robert, primary, Rogiers, Aljosja, primary, Xu, Hang, primary, Huebner, Ariana, primary, McGranahan, Nicholas, primary, Al Bakir, Maise, primary, Murai, Jun, primary, Naceur-Lombardelli, Cristina, primary, Borg, Elaine, primary, Mitchison, Miriam, primary, Moore, David A., primary, Falzon, Mary, primary, Proctor, Ian, primary, Stamp, Gordon W.H., primary, Nye, Emma L., primary, Young, Kate, primary, Furness, Andrew J.S., primary, Pickering, Lisa, primary, Stewart, Ruby, primary, Mahadeva, Ula, primary, Green, Anna, primary, Larkin, James, primary, Litchfield, Kevin, primary, Swanton, Charles, primary, Jamal-Hanjani, Mariam, primary, and Turajlic, Samra, primary

Published
2023
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24. Supplementary Tables S1-S8 from Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

Author

Spain, Lavinia, primary, Coulton, Alexander, primary, Lobon, Irene, primary, Rowan, Andrew, primary, Schnidrig, Desiree, primary, Shepherd, Scott T.C., primary, Shum, Benjamin, primary, Byrne, Fiona, primary, Goicoechea, Maria, primary, Piperni, Elisa, primary, Au, Lewis, primary, Edmonds, Kim, primary, Carlyle, Eleanor, primary, Hunter, Nikki, primary, Renn, Alexandra, primary, Messiou, Christina, primary, Hughes, Peta, primary, Nobbs, Jaime, primary, Foijer, Floris, primary, van den Bos, Hilda, primary, Wardenaar, Rene, primary, Spierings, Diana C.J., primary, Spencer, Charlotte, primary, Schmitt, Andreas M., primary, Tippu, Zayd, primary, Lingard, Karla, primary, Grostate, Lauren, primary, Peat, Kema, primary, Kelly, Kayleigh, primary, Sarker, Sarah, primary, Vaughan, Sarah, primary, Mangwende, Mary, primary, Terry, Lauren, primary, Kelly, Denise, primary, Biano, Jennifer, primary, Murra, Aida, primary, Korteweg, Justine, primary, Lewis, Charlotte, primary, O'Flaherty, Molly, primary, Cattin, Anne-Laure, primary, Emmerich, Max, primary, Gerard, Camille L., primary, Pallikonda, Husayn Ahmed, primary, Lynch, Joanna, primary, Mason, Robert, primary, Rogiers, Aljosja, primary, Xu, Hang, primary, Huebner, Ariana, primary, McGranahan, Nicholas, primary, Al Bakir, Maise, primary, Murai, Jun, primary, Naceur-Lombardelli, Cristina, primary, Borg, Elaine, primary, Mitchison, Miriam, primary, Moore, David A., primary, Falzon, Mary, primary, Proctor, Ian, primary, Stamp, Gordon W.H., primary, Nye, Emma L., primary, Young, Kate, primary, Furness, Andrew J.S., primary, Pickering, Lisa, primary, Stewart, Ruby, primary, Mahadeva, Ula, primary, Green, Anna, primary, Larkin, James, primary, Litchfield, Kevin, primary, Swanton, Charles, primary, Jamal-Hanjani, Mariam, primary, and Turajlic, Samra, primary

Published
2023
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25. Supplementary Figures S1-S25 from Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

Author

Spain, Lavinia, primary, Coulton, Alexander, primary, Lobon, Irene, primary, Rowan, Andrew, primary, Schnidrig, Desiree, primary, Shepherd, Scott T.C., primary, Shum, Benjamin, primary, Byrne, Fiona, primary, Goicoechea, Maria, primary, Piperni, Elisa, primary, Au, Lewis, primary, Edmonds, Kim, primary, Carlyle, Eleanor, primary, Hunter, Nikki, primary, Renn, Alexandra, primary, Messiou, Christina, primary, Hughes, Peta, primary, Nobbs, Jaime, primary, Foijer, Floris, primary, van den Bos, Hilda, primary, Wardenaar, Rene, primary, Spierings, Diana C.J., primary, Spencer, Charlotte, primary, Schmitt, Andreas M., primary, Tippu, Zayd, primary, Lingard, Karla, primary, Grostate, Lauren, primary, Peat, Kema, primary, Kelly, Kayleigh, primary, Sarker, Sarah, primary, Vaughan, Sarah, primary, Mangwende, Mary, primary, Terry, Lauren, primary, Kelly, Denise, primary, Biano, Jennifer, primary, Murra, Aida, primary, Korteweg, Justine, primary, Lewis, Charlotte, primary, O'Flaherty, Molly, primary, Cattin, Anne-Laure, primary, Emmerich, Max, primary, Gerard, Camille L., primary, Pallikonda, Husayn Ahmed, primary, Lynch, Joanna, primary, Mason, Robert, primary, Rogiers, Aljosja, primary, Xu, Hang, primary, Huebner, Ariana, primary, McGranahan, Nicholas, primary, Al Bakir, Maise, primary, Murai, Jun, primary, Naceur-Lombardelli, Cristina, primary, Borg, Elaine, primary, Mitchison, Miriam, primary, Moore, David A., primary, Falzon, Mary, primary, Proctor, Ian, primary, Stamp, Gordon W.H., primary, Nye, Emma L., primary, Young, Kate, primary, Furness, Andrew J.S., primary, Pickering, Lisa, primary, Stewart, Ruby, primary, Mahadeva, Ula, primary, Green, Anna, primary, Larkin, James, primary, Litchfield, Kevin, primary, Swanton, Charles, primary, Jamal-Hanjani, Mariam, primary, and Turajlic, Samra, primary

Published
2023
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26. Escape from nonsense-mediated decay associates with anti-tumor immunogenicity

Author

Litchfield, Kevin, Reading, James L., Lim, Emilia L., Xu, Hang, Liu, Po, Al-Bakir, Maise, Wong, Yien Ning Sophia, Rowan, Andrew, Funt, Samuel A., Merghoub, Taha, Perkins, David, Lauss, Martin, Svane, Inge Marie, Jönsson, Göran, Herrero, Javier, Larkin, James, Quezada, Sergio A., Hellmann, Matthew D., Turajlic, Samra, and Swanton, Charles

Published
2020
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28. Contributors

Author

Austin, Christopher P., primary, Balls, Michael, additional, Blaauboer, Bas J., additional, Botham, Philip, additional, Burt, Tal, additional, Casey, Warren, additional, Červinka, Miroslav, additional, Cheng, Shujun, additional, Combes, Robert D., additional, Corvi, Raffaella, additional, Cronin, Mark T.D., additional, Curren, Rodger D., additional, De Angelis, Isabella, additional, Dehne, Eva-Maria, additional, Doe, John, additional, Eskes, Chantra, additional, Feigenbaum, Alexandre, additional, Forgacs, Zsolt, additional, Forsby, Anna, additional, France, Malcolm P., additional, Freeman Bain, Simon A., additional, Goldberg, Alan, additional, Gruber, Franz P., additional, Guillouzo, André, additional, Hartung, Thomas, additional, Heinonen, Tuula, additional, Hickman, James, additional, Hill, Erin H., additional, Imai, Koichi, additional, Kandarova, Helena, additional, Kavlock, Robert J., additional, Kenna, J Gerry, additional, Knudsen, Lisbeth E., additional, Kojima, Hajime, additional, Kolar, Roman, additional, Leist, Marcel, additional, Lidbury, Brett A., additional, Lowit, Anna, additional, Minor, Philip, additional, Pfaller, Walter, additional, Prieto, Pilar, additional, Ram, Rebecca, additional, Repetto, Guillermo, additional, Rogiers, Vera, additional, Roi, Annett J., additional, Rowan, Andrew, additional, Sakai, Yasuyuki, additional, Sesardic, Thea, additional, Shuler, Michael, additional, Śladowski, Dariusz, additional, Spielmann, Horst, additional, Stephens, Martin L., additional, Tähti, Hanna, additional, Tanaka, Noriho, additional, Testai, Emanuela, additional, Tice, Raymond R., additional, Trigwell, Susan, additional, Verfaillie, Catherine, additional, von Aulock, Sonja, additional, Worth, Andrew P., additional, Yoon, Miyoung, additional, and Zuang, Valérie, additional

Published
2019
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31. Abstract 4277: Measuring proliferation rates of distinct tumour clones using single-cell DNA sequencing

Author

Lucas, Olivia, primary, Ward, Sophie, additional, Zaidi, Rija, additional, Hill, Mark, additional, Lim, Emilia, additional, Zhai, Haoran, additional, Bunkum, Abigail, additional, Hessey, Sonya, additional, Dietzen, Michelle, additional, Rowan, Andrew, additional, Naceur-Lombardelli, Cristina, additional, Kanu, Nnenna, additional, Jamal-Hanjani, Mariam, additional, Swanton, Charles, additional, and Zaccaria, Simone, additional

Published
2023
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32. Data from Tracking the Genomic Evolution of Esophageal Adenocarcinoma through Neoadjuvant Chemotherapy

Author

Murugaesu, Nirupa, primary, Wilson, Gareth A., primary, Birkbak, Nicolai J., primary, Watkins, Thomas B.K., primary, McGranahan, Nicholas, primary, Kumar, Sacheen, primary, Abbassi-Ghadi, Nima, primary, Salm, Max, primary, Mitter, Richard, primary, Horswell, Stuart, primary, Rowan, Andrew, primary, Phillimore, Benjamin, primary, Biggs, Jennifer, primary, Begum, Sharmin, primary, Matthews, Nik, primary, Hochhauser, Daniel, primary, Hanna, George B., primary, and Swanton, Charles, primary

Published
2023
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33. 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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34. 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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35. Supplementary Table S3 from Tracking the Genomic Evolution of Esophageal Adenocarcinoma through Neoadjuvant Chemotherapy

Author

Murugaesu, Nirupa, primary, Wilson, Gareth A., primary, Birkbak, Nicolai J., primary, Watkins, Thomas B.K., primary, McGranahan, Nicholas, primary, Kumar, Sacheen, primary, Abbassi-Ghadi, Nima, primary, Salm, Max, primary, Mitter, Richard, primary, Horswell, Stuart, primary, Rowan, Andrew, primary, Phillimore, Benjamin, primary, Biggs, Jennifer, primary, Begum, Sharmin, primary, Matthews, Nik, primary, Hochhauser, Daniel, primary, Hanna, George B., primary, and Swanton, Charles, primary

Published
2023
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36. 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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37. 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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38. Supplementary Methods, Tables S1 - S2, S4, Figures S1 - S11 from Tracking the Genomic Evolution of Esophageal Adenocarcinoma through Neoadjuvant Chemotherapy

Author

Murugaesu, Nirupa, primary, Wilson, Gareth A., primary, Birkbak, Nicolai J., primary, Watkins, Thomas B.K., primary, McGranahan, Nicholas, primary, Kumar, Sacheen, primary, Abbassi-Ghadi, Nima, primary, Salm, Max, primary, Mitter, Richard, primary, Horswell, Stuart, primary, Rowan, Andrew, primary, Phillimore, Benjamin, primary, Biggs, Jennifer, primary, Begum, Sharmin, primary, Matthews, Nik, primary, Hochhauser, Daniel, primary, Hanna, George B., primary, and Swanton, Charles, primary

Published
2023
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39. Supplementary Table S2 from APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability

Author

Sansregret, Laurent, primary, Patterson, James O., primary, Dewhurst, Sally, primary, López-García, Carlos, primary, Koch, André, primary, McGranahan, Nicholas, primary, Chao, William Chong Hang, primary, Barry, David J., primary, Rowan, Andrew, primary, Instrell, Rachael, primary, Horswell, Stuart, primary, Way, Michael, primary, Howell, Michael, primary, Singleton, Martin R., primary, Medema, René H., primary, Nurse, Paul, primary, Petronczki, Mark, primary, and Swanton, Charles, primary

Published
2023
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40. Data from APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability

Author

Sansregret, Laurent, primary, Patterson, James O., primary, Dewhurst, Sally, primary, López-García, Carlos, primary, Koch, André, primary, McGranahan, Nicholas, primary, Chao, William Chong Hang, primary, Barry, David J., primary, Rowan, Andrew, primary, Instrell, Rachael, primary, Horswell, Stuart, primary, Way, Michael, primary, Howell, Michael, primary, Singleton, Martin R., primary, Medema, René H., primary, Nurse, Paul, primary, Petronczki, Mark, primary, and Swanton, Charles, primary

Published
2023
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41. 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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42. 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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43. 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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44. Supplementary Figure Legends, Table Legends from APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability

Author

Sansregret, Laurent, primary, Patterson, James O., primary, Dewhurst, Sally, primary, López-García, Carlos, primary, Koch, André, primary, McGranahan, Nicholas, primary, Chao, William Chong Hang, primary, Barry, David J., primary, Rowan, Andrew, primary, Instrell, Rachael, primary, Horswell, Stuart, primary, Way, Michael, primary, Howell, Michael, primary, Singleton, Martin R., primary, Medema, René H., primary, Nurse, Paul, primary, Petronczki, Mark, primary, and Swanton, Charles, primary

Published
2023
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45. 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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46. 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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47. Supplementary Figures S1 - S10 from APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability

Author

Sansregret, Laurent, primary, Patterson, James O., primary, Dewhurst, Sally, primary, López-García, Carlos, primary, Koch, André, primary, McGranahan, Nicholas, primary, Chao, William Chong Hang, primary, Barry, David J., primary, Rowan, Andrew, primary, Instrell, Rachael, primary, Horswell, Stuart, primary, Way, Michael, primary, Howell, Michael, primary, Singleton, Martin R., primary, Medema, René H., primary, Nurse, Paul, primary, Petronczki, Mark, primary, and Swanton, Charles, primary

Published
2023
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48. 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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49. 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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50. 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
Full Text
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