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298 results on '"Dudderidge, Tim"'

2. The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET): A Systematic Review and International Consensus Recommendations

Author

Light, Alexander, Mayor, Nikhil, Cullen, Emma, Kirkham, Alex, Padhani, Anwar R., Arya, Manit, Bomers, Joyce G.R., Dudderidge, Tim, Ehdaie, Behfar, Freeman, Alex, Guillaumier, Stephanie, Hindley, Richard, Lakhani, Amish, Pendse, Douglas, Punwani, Shonit, Rastinehad, Ardeshir R., Rouvière, Olivier, Sanchez-Salas, Rafael, Schoots, Ivo G., Sokhi, Heminder K., Tam, Henry, Tempany, Clare M., Valerio, Massimo, Verma, Sadhna, Villeirs, Geert, van der Meulen, Jan, Ahmed, Hashim U., and Shah, Taimur T.

Published
2024
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3. The Role of Multiparametric MRI and MRI–targeted Biopsy in the Diagnosis of Radiorecurrent Prostate Cancer: An Analysis from the FORECAST Trial

Author

Light, Alexander, Kanthabalan, Abi, Otieno, Marjorie, Pavlou, Menelaos, Omar, Rumana, Adeleke, Sola, Giganti, Francesco, Brew-Graves, Chris, Williams, Norman R., Emara, Amr, Haroon, Athar, Latifoltojar, Arash, Sidhu, Harbir, Freeman, Alex, Orczyk, Clement, Nikapota, Ashok, Dudderidge, Tim, Hindley, Richard G., Virdi, Jaspal, Arya, Manit, Payne, Heather, Mitra, Anita V., Bomanji, Jamshed, Winkler, Mathias, Horan, Gail, Moore, Caroline M., Emberton, Mark, Punwani, Shonit, Ahmed, Hashim U., and Shah, Taimur T.

Published
2024
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6. Magnetic Resonance Imaging and Targeted Biopsies Compared to Transperineal Mapping Biopsies Before Focal Ablation in Localised and Metastatic Recurrent Prostate Cancer After Radiotherapy

Author

Shah, Taimur T., Kanthabalan, Abi, Otieno, Marjorie, Pavlou, Menelaos, Omar, Rumana, Adeleke, Sola, Giganti, Francesco, Brew-Graves, Chris, Williams, Norman R., Grierson, Jack, Miah, Haroon, Emara, Amr, Haroon, Athar, Latifoltojar, Arash, Sidhu, Harbir, Clemente, Joey, Freeman, Alex, Orczyk, Clement, Nikapota, Ashok, Dudderidge, Tim, Hindley, Richard G., Virdi, Jaspal, Arya, Manit, Payne, Heather, Mitra, Anita, Bomanji, Jamshed, Winkler, Mathias, Horan, Gail, Moore, Caroline M., Emberton, Mark, Punwani, Shonit, and Ahmed, Hashim U.

Published
2022
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7. Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience

Author

Reddy, Deepika, Peters, Max, Shah, Taimur T., van Son, Marieke, Tanaka, Mariana Bertoncelli, Huber, Philipp M., Lomas, Derek, Rakauskas, Arnas, Miah, Saiful, Eldred-Evans, David, Guillaumier, Stephanie, Hosking-Jervis, Feargus, Engle, Ryan, Dudderidge, Tim, Hindley, Richard G., Emara, Amr, Nigam, Raj, McCartan, Neil, Valerio, Massimo, Afzal, Naveed, Lewi, Henry, Orczyk, Clement, Ogden, Chris, Shergill, Iqbal, Persad, Raj, Virdi, Jaspal, Moore, Caroline M., Arya, Manit, Winkler, Mathias, Emberton, Mark, and Ahmed, Hashim U.

Published
2022
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9. Conventional radical versus focal treatment for localised prostate cancer: a propensity score weighted comparison of 6-year tumour control

Author

van Son, Marieke J., Peters, Max, Reddy, Deepika, Shah, Taimur T., Hosking-Jervis, Feargus, Robinson, Stephen, Lagendijk, Jan J. W., Mangar, Stephen, Dudderidge, Tim, McCracken, Stuart, Hindley, Richard G., Emara, Amr, Nigam, Raj, Persad, Raj, Virdi, Jaspal, Lewi, Henry, Moore, Caroline, Orczyk, Clement, Emberton, Mark, Arya, Manit, Ahmed, Hashim U., van der Voort van Zyp, Jochem R. N., Winkler, Matt, and Falconer, Alison

Published
2021
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10. Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Author

Wedge, David C, Gundem, Gunes, Mitchell, Thomas, Woodcock, Dan J, Martincorena, Inigo, Ghori, Mohammed, Zamora, Jorge, Butler, Adam, Whitaker, Hayley, Kote-Jarai, Zsofia, Alexandrov, Ludmil B, Van Loo, Peter, Massie, Charlie E, Dentro, Stefan, Warren, Anne Y, Verrill, Clare, Berney, Dan M, Dennis, Nening, Merson, Sue, Hawkins, Steve, Howat, William, Lu, Yong-Jie, Lambert, Adam, Kay, Jonathan, Kremeyer, Barbara, Karaszi, Katalin, Luxton, Hayley, Camacho, Niedzica, Marsden, Luke, Edwards, Sandra, Matthews, Lucy, Bo, Valeria, Leongamornlert, Daniel, McLaren, Stuart, Ng, Anthony, Yu, Yongwei, Zhang, Hongwei, Dadaev, Tokhir, Thomas, Sarah, Easton, Douglas F, Ahmed, Mahbubl, Bancroft, Elizabeth, Fisher, Cyril, Livni, Naomi, Nicol, David, Tavaré, Simon, Gill, Pelvender, Greenman, Christopher, Khoo, Vincent, Van As, Nicholas, Kumar, Pardeep, Ogden, Christopher, Cahill, Declan, Thompson, Alan, Mayer, Erik, Rowe, Edward, Dudderidge, Tim, Gnanapragasam, Vincent, Shah, Nimish C, Raine, Keiran, Jones, David, Menzies, Andrew, Stebbings, Lucy, Teague, Jon, Hazell, Steven, Corbishley, Cathy, CAMCAP Study Group, de Bono, Johann, Attard, Gerhardt, Isaacs, William, Visakorpi, Tapio, Fraser, Michael, Boutros, Paul C, Bristow, Robert G, Workman, Paul, Sander, Chris, The TCGA Consortium, Hamdy, Freddie C, Futreal, Andrew, McDermott, Ultan, Al-Lazikani, Bissan, Lynch, Andrew G, Bova, G Steven, Foster, Christopher S, Brewer, Daniel S, Neal, David E, Cooper, Colin S, and Eeles, Rosalind A

Subjects
Genetics, Human Genome, Aging, Cancer, Urologic Diseases, Biotechnology, Prostate Cancer, Aetiology, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, Adult, Aged, Aged, 80 and over, BRCA2 Protein, Disease Progression, Hepatocyte Nuclear Factor 3-alpha, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Mutation, Oncogenes, Prostatic Neoplasms, CAMCAP Study Group, TCGA Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials.

Published
2018

12. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study

Author

Adams, Lisa, Adlard, Julian, Alfonso, Rosa, Ali, Saira, Andrew, Angela, Araújo, Luís, Azam, Nazya, Ball, Darran, Barker, Queenstone, Basevitch, Alon, Benton, Barbara, Berlin, Cheryl, Bermingham, Nicola, Biller, Leah, Bloss, Angela, Bradford, Matilda, Bradshaw, Nicola, Branson, Amy, Brendler, Charles, Brennan, Maria, Bulman, Barbara, Burgess, Lucy, Cahill, Declan, Callard, Alice, Calvo Verges, Nuria, Cardoso, Marta, Carter, Vanda, Catanzaro, Mario, Chamberlain, Anthony, Chapman, Cyril, Chong, Michael, Clark, Caroline, Clowes, Virginia, Cogley, Lyn, Cole, Trevor, Compton, Cecilia, Conner, Tom, Cookson, Sandra, Cornford, Philip, Costello, Philandra, Coulier, Laura, Davies, Michaela, Dechet, Christopher, DeSouza, Bianca, Devlin, Gemma, Douglas, Fiona, Douglas, Emma, Dudakia, Darshna, Duncan, Alexis, Ellery, Natalie, Everest, Sarah, Freemantle, Sue, Frydenberg, Mark, Fuller, Debbie, Gabriel, Camila, Gale, Madeline, Garcia, Lynda, Gay, Simona, Genova, Elena, George, Angela, Georgiou, Demetra, Gisbert, Alexandra, Gleeson, Margaret, Glover, Wayne, Gnanapragasam, Vincent, Goff, Sally, Goldgar, David, Gonçalves, Nuno, Goodman, Selina, Gorrie, Jennifer, Gott, Hannah, Grant, Anna, Gray, Catherine, Griffiths, Julie, Gupwell, Karin, Gurasashvili, Jana, Hanslien, Eldbjørg, Haraldsdottir, Sigurdis, Hart, Rachel, Hartigan, Catherine, Hawkes, Lara, Heaton, Tricia, Henderson, Alex, Henrique, Rui, Hilario, Kathrine, Hill, Kathryn, Hulick, Peter, Hunt, Clare, Hutchings, Melanie, Ibitoye, Rita, Inglehearn, Thomas, Ireland, Joanna, Islam, Farah, Ismail, Siti, Jacobs, Chris, James, Denzil, Jenkins, Sharon, Jobson, Irene, Johnstone, Anne, Jones, Oliver, Josefsberg Ben-Yehoshua, Sagi, Kaemba, Beckie, Kaul, Karen, Kemp, Zoe, Kinsella, Netty, Klehm, Margaret, Kockelbergh, Roger, Kohut, Kelly, Kosicka-Slawinska, Monika, Kulkarni, Anjana, Kumar, Pardeep, Lam, Jimmy, LeButt, Mandy, Leibovici, Dan, Lim, Ramona, Limb, Lauren, Lomas, Claire, Longmuir, Mark, López, Consol, Magnani, Tiziana, Maia, Sofia, Maiden, Jessica, Male, Alison, Manalo, Merrie, Martin, Phoebe, McBride, Donna, McGuire, Michael, McMahon, Romayne, McNally, Claire, McVeigh, Terri, Melzer, Ehud, Mencias, Mark, Mercer, Catherine, Mitchell, Gillian, Mora, Josefina, Morton, Catherine, Moss, Cathryn, Murphy, Morgan, Murphy, Declan, Mzazi, Shumi, Nadolski, Maria, Newlin, Anna, Nogueira, Pedro, O'Keefe, Rachael, O'Toole, Karen, O'Connell, Shona, Ogden, Chris, Okoth, Linda, Oliveira, Jorge, Paez, Edgar, Palou, Joan, Park, Linda, Patel, Nafisa, Paulo Souto, João, Pearce, Allison, Peixoto, Ana, Perez, Kimberley, Petelin, Lara, Pichert, Gabriella, Poile, Charlotte, Potter, Alison, Preitner, Nadia, Purnell, Helen, Quinn, Ellen, Radice, Paolo, Rankin, Brigette, Rees, Katie, Renton, Caroline, Richardson, Kate, Risby, Peter, Rogers, Jason, Ruderman, Maggie, Ruiz, April, Sajoo, Anaar, Salvatore, Natale, Sands, Victoria, Sanguedolce, Francesco, Sattar, Ayisha, Saunders, Kathryn, Schofield, Lyn, Scott, Rodney, Searle, Anne, Sehra, Ravinder, Selkirk, Christina, Shackleton, Kylie, Shanley, Sue, Shaw, Adam, Shevrin, Daniel, Shipman, Hannah, Sidat, Zahirah, Siguake, Kas, Simon, Kate, Smyth, Courtney, Snadden, Lesley, Solanky, Nita, Solomons, Joyce, Sorrentino, Margherita, Stayner, Barbara, Stephenson, Robert, Stoffel, Elena, Thomas, Maggie, Thompson, Alan, Tidey, Lizzie, Tischkowitz, Marc, Torokwa, Audrey, Townshend, Sharron, Treherne, Katy, Tricker, Karen, Trinh, Quoc-Dien, Tripathi, Vishakha, Turnbull, Clare, Valdagni, Riccardo, Van As, Nicholas, Venne, Vickie, Verdon, Lizzie, Vitellaro, Marco, Vogel, Kristen, Walker, Lisa, Watford, Amy, Watt, Cathy, Weintroub, Ilana, Weiss, Shelly, Weissman, Scott, Weston, Michelle, Wiggins, Jennifer, Wise, Gillian, Woodhouse, Christopher, Yesildag, Pembe, Youngs, Alice, Yurgelun, Matthew, Zollo, Fabiana, Bancroft, Elizabeth K, Page, Elizabeth C, Brook, Mark N, Thomas, Sarah, Taylor, Natalie, Pope, Jennifer, McHugh, Jana, Jones, Ann-Britt, Karlsson, Questa, Merson, Susan, Ong, Kai Ren, Hoffman, Jonathan, Huber, Camilla, Maehle, Lovise, Grindedal, Eli Marie, Stormorken, Astrid, Evans, D Gareth, Rothwell, Jeanette, Lalloo, Fiona, Brady, Angela F, Bartlett, Marion, Snape, Katie, Hanson, Helen, James, Paul, McKinley, Joanne, Mascarenhas, Lyon, Syngal, Sapna, Ukaegbu, Chinedu, Side, Lucy, Thomas, Tessy, Barwell, Julian, Teixeira, Manuel R, Izatt, Louise, Suri, Mohnish, Macrae, Finlay A, Poplawski, Nicola, Chen-Shtoyerman, Rakefet, Ahmed, Munaza, Musgrave, Hannah, Nicolai, Nicola, Greenhalgh, Lynn, Brewer, Carole, Pachter, Nicholas, Spigelman, Allan D, Azzabi, Ashraf, Helfand, Brian T, Halliday, Dorothy, Buys, Saundra, Ramon y Cajal, Teresa, Donaldson, Alan, Cooney, Kathleen A, Harris, Marion, McGrath, John, Davidson, Rosemarie, Taylor, Amy, Cooke, Peter, Myhill, Kathryn, Hogben, Matthew, Aaronson, Neil K, Ardern-Jones, Audrey, Bangma, Chris H, Castro, Elena, Dearnaley, David, Dias, Alexander, Dudderidge, Tim, Eccles, Diana M, Green, Kate, Eyfjord, Jorunn, Falconer, Alison, Foster, Christopher S, Gronberg, Henrik, Hamdy, Freddie C, Johannsson, Oskar, Khoo, Vincent, Lilja, Hans, Lindeman, Geoffrey J, Lubinski, Jan, Axcrona, Karol, Mikropoulos, Christos, Mitra, Anita V, Moynihan, Clare, Ni Raghallaigh, Holly, Rennert, Gad, Collier, Rebecca, Offman, Judith, Kote-Jarai, Zsofia, and Eeles, Rosalind A

Published
2021
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14. Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study

Author

Shah, Taimur T., Reddy, Deepika, Peters, Max, Ball, Daniel, Kim, Na Hyun, Gomez, Enrique Gomez, Miah, Saiful, Evans, David Eldred, Guillaumier, Stephanie, van Rossum, Peter S. N., Van Son, Marieke J., Hosking-Jervis, Feargus, Dudderidge, Tim, Hindley, Richard, Emara, Amr, McCracken, Stuart, Greene, Damian, Nigam, Raj, McCartan, Neil, Valerio, Massimo, Minhas, Suks, Afzal, Naveed, Lewi, Henry, Ogden, Chris, Persad, Raj, Virdi, Jaspal, Moore, Caroline M., Arya, Manit, Emberton, Mark, Ahmed, Hashim U., and Winkler, Mathias

Published
2021
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15. The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET):A Systematic Review and International Consensus Recommendations

Author

Light, Alexander, Mayor, Nikhil, Cullen, Emma, Kirkham, Alex, Padhani, Anwar R., Arya, Manit, Bomers, Joyce G.R., Dudderidge, Tim, Ehdaie, Behfar, Freeman, Alex, Guillaumier, Stephanie, Hindley, Richard, Lakhani, Amish, Pendse, Douglas, Punwani, Shonit, Rastinehad, Ardeshir R., Rouvière, Olivier, Sanchez-Salas, Rafael, Schoots, Ivo G., Sokhi, Heminder K., Tam, Henry, Tempany, Clare M., Valerio, Massimo, Verma, Sadhna, Villeirs, Geert, van der Meulen, Jan, Ahmed, Hashim U., Shah, Taimur T., Light, Alexander, Mayor, Nikhil, Cullen, Emma, Kirkham, Alex, Padhani, Anwar R., Arya, Manit, Bomers, Joyce G.R., Dudderidge, Tim, Ehdaie, Behfar, Freeman, Alex, Guillaumier, Stephanie, Hindley, Richard, Lakhani, Amish, Pendse, Douglas, Punwani, Shonit, Rastinehad, Ardeshir R., Rouvière, Olivier, Sanchez-Salas, Rafael, Schoots, Ivo G., Sokhi, Heminder K., Tam, Henry, Tempany, Clare M., Valerio, Massimo, Verma, Sadhna, Villeirs, Geert, van der Meulen, Jan, Ahmed, Hashim U., and Shah, Taimur T.

Abstract

Background and objective: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. Methods:A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. Key findings and limitations: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-w

Published
2024

17. Feasibility of Comparative Health Research Outcome of Novel Surgery in prostate cancer (IP4-CHRONOS): statistical analysis plan for the randomised feasibility phase of the CHRONOS study

Author

Day, Emily, Prevost, A. Toby, Sydes, Matthew R., Reddy, Deepika, Shah, Taimur T., Winkler, Mathias, Dudderidge, Tim, Staffurth, John, McCracken, Stuart, Khoo, Vincent, Jadav, Puja, Klimowska-Nassar, Natalia, Sasikaran, Thiagarajah, Ahmed, Hashim U., and Fiorentino, Francesca

Published
2021
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18. Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue

Author

Cooper, Colin S, Eeles, Rosalind, Wedge, David C, Van Loo, Peter, Gundem, Gunes, Alexandrov, Ludmil B, Kremeyer, Barbara, Butler, Adam, Lynch, Andrew G, Camacho, Niedzica, Massie, Charlie E, Kay, Jonathan, Luxton, Hayley J, Edwards, Sandra, Kote-Jarai, Zsofia, Dennis, Nening, Merson, Sue, Leongamornlert, Daniel, Zamora, Jorge, Corbishley, Cathy, Thomas, Sarah, Nik-Zainal, Serena, Ramakrishna, Manasa, O'Meara, Sarah, Matthews, Lucy, Clark, Jeremy, Hurst, Rachel, Mithen, Richard, Bristow, Robert G, Boutros, Paul C, Fraser, Michael, Cooke, Susanna, Raine, Keiran, Jones, David, Menzies, Andrew, Stebbings, Lucy, Hinton, Jon, Teague, Jon, McLaren, Stuart, Mudie, Laura, Hardy, Claire, Anderson, Elizabeth, Joseph, Olivia, Goody, Victoria, Robinson, Ben, Maddison, Mark, Gamble, Stephen, Greenman, Christopher, Berney, Dan, Hazell, Steven, Livni, Naomi, Fisher, Cyril, Ogden, Christopher, Kumar, Pardeep, Thompson, Alan, Woodhouse, Christopher, Nicol, David, Mayer, Erik, Dudderidge, Tim, Shah, Nimish C, Gnanapragasam, Vincent, Voet, Thierry, Campbell, Peter, Futreal, Andrew, Easton, Douglas, Warren, Anne Y, Foster, Christopher S, Stratton, Michael R, Whitaker, Hayley C, McDermott, Ultan, Brewer, Daniel S, and Neal, David E

Subjects
Human Genome, Urologic Diseases, Prevention, Genetics, Prostate Cancer, Cancer, Aging, Case-Control Studies, Cell Lineage, Clonal Evolution, Clone Cells, DNA Mutational Analysis, Humans, Male, Mutation, Neoplasms, Multiple Primary, Phylogeny, Prostate, Prostatic Neoplasms, ICGC Prostate Group, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

Published
2015

19. The role of DNA replication licensing proteins in urological cancer management

Author

Dudderidge, Tim

Subjects
616.994
Abstract

The non-invasive diagnosis of cancer and assessment of disease severity are both important challenges facing urologists managing patients with kidney, bladder and prostate cancer. Both challenges can potentially be met through the use of molecular markers of cancer that are present in blood, urine and biopsy material from tumours. In this thesis I explore the use of DNA replication licensing proteins, key components of the DNA replication machinery, as diagnostic, prognostic and predictive factors for urological cancers. The main markers studied, Mcm2, McmS and geminin are crucially important as their expression is closely linked with cell cycle activation and control in normal and malignant cells. Loss of growth control rapidly leads to abnormal expression of these proteins. Furthermore, by combined analysis with the well-known cell cycle marker Ki67, we have learned more about the cell cycle kinetics in urological tumours. The studies in this thesis include the examination of DNA replication licensing protein expression in kidney and prostate cancer tissue. In the study of kidney cancer, my coworkers and I examined a series of tumours from patients who had undergone nephrectomy for renal cell carcinoma. We showed that increased Mcm2 expression is associated with reduced disease-free survival time and that Ki67 is an independent predictor of disease free survival in this disease. In prostate cancer we investigated linkages between the MEKS/ERKS pathway and DNA replication licensing during prostate carcinogenesis. We confirmed that dysregulation of upstream pathways leads 8 to increased expression of DNA replication licensing proteins. Importantly, we showed that Mcm2 was an independent prognostic marker in prostate cancer. The latter two studies examine the use of Mcm5 as a urinary diagnostic marker for prostate and bladder cancer. We were able to demonstrate that in a series of men at a variety of stages of prostate cancer, elevated urinary Mcm5 levels were present in a very large proportion of men with prostate cancer and mostly absent in patients with a benign diagnosis (82% sensitivity, 73-93% specificity). In a much larger study, the largest to date to evaluate a commercialized comparative marker NMP22, we determined that the academic Mcm5 assay was a highly accurate diagnostic marker for bladder cancer. Interestingly, we found that the combination of Mcm5 with NMP22 improved the detection of bladder cancer and allowed the identification of95% of patients with clinically significant disease. In the discussion section ofthis thesis I conclude that the DNA replication licensing proteins offer researchers a number opportunities to develop diagnostic and predictive markers for urological cancer. Clinical trials of a commercialized Mcm5 assay (UrosensTM) are underway and may lead to novel minimally invasive approaches to urological cancer detection.

Published
2014

20. Focal therapy versus radical prostatectomy and external beam radiotherapy as primary treatment options for non-metastatic prostate cancer: results of a cost-effectiveness analysis

Author

Reddy, Deepika, primary, van Son, Marieke, additional, Peters, Max, additional, Bertoncelli Tanaka, Mariana, additional, Dudderidge, Tim, additional, Cullen, Emma, additional, Ho, Carmen Lok Tung, additional, Hindley, Richard G., additional, Emara, Amr, additional, McCracken, Stuart, additional, Orczyk, Clement, additional, Shergill, Iqbal, additional, Mangar, Stephen, additional, Nigam, Raj, additional, Virdi, Jaspal, additional, Moore, Caroline M., additional, Arya, Manit, additional, Shah, Taimur T., additional, Winkler, Mathias, additional, Emberton, Mark, additional, Falconer, Alison, additional, Belsey, Jonathan, additional, and Ahmed, Hashim U., additional

Published
2023
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21. The Role of Multiparametric MRI and MRI–targeted Biopsy in the Diagnosis of Radiorecurrent Prostate Cancer: An Analysis from the FORECAST Trial

Author

Light, Alexander, primary, Kanthabalan, Abi, additional, Otieno, Marjorie, additional, Pavlou, Menelaos, additional, Omar, Rumana, additional, Adeleke, Sola, additional, Giganti, Francesco, additional, Brew-Graves, Chris, additional, Williams, Norman R., additional, Emara, Amr, additional, Haroon, Athar, additional, Latifoltojar, Arash, additional, Sidhu, Harbir, additional, Freeman, Alex, additional, Orczyk, Clement, additional, Nikapota, Ashok, additional, Dudderidge, Tim, additional, Hindley, Richard G., additional, Virdi, Jaspal, additional, Arya, Manit, additional, Payne, Heather, additional, Mitra, Anita V., additional, Bomanji, Jamshed, additional, Winkler, Mathias, additional, Horan, Gail, additional, Moore, Caroline M., additional, Emberton, Mark, additional, Punwani, Shonit, additional, Ahmed, Hashim U., additional, and Shah, Taimur T., additional

Published
2023
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22. External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

Author

Light, Alexander, primary, Peters, Max, additional, Reddy, Deepika, additional, Kanthabalan, Abi, additional, Otieno, Marjorie, additional, Pavlou, Menelaos, additional, Omar, Rumana, additional, Adeleke, Sola, additional, Giganti, Francesco, additional, Brew‐Graves, Chris, additional, Williams, Norman R., additional, Emara, Amr, additional, Haroon, Athar, additional, Latifoltojar, Arash, additional, Sidhu, Harbir, additional, Freeman, Alex, additional, Orczyk, Clement, additional, Nikapota, Ashok, additional, Dudderidge, Tim, additional, Hindley, Richard G., additional, Virdi, Jaspal, additional, Arya, Manit, additional, Payne, Heather, additional, Mitra, Anita V., additional, Bomanji, Jamshed, additional, Winkler, Mathias, additional, Horan, Gail, additional, Moore, Caroline, additional, Emberton, Mark, additional, Punwani, Shonit, additional, Ahmed, Hashim U., additional, and Shah, Taimur T., additional

Published
2023
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23. A critical evaluation of visual proportion of Gleason 4 and maximum cancer core length quantified by histopathologists

Author

Carmona Echeverria, Lina Maria, Haider, Aiman, Freeman, Alex, Stopka-Farooqui, Urszula, Rosenfeld, Avi, Simpson, Benjamin S., Hu, Yipeng, Hawkes, David, Pye, Hayley, Heavey, Susan, Stavrinides, Vasilis, Norris, Joseph M., Bosaily, Ahmed El-Shater, Cardona Barrena, Cristina, Bott, Simon, Brown, Louise, Burns-Cox, Nick, Dudderidge, Tim, Henderson, Alastair, Hindley, Richard, Kaplan, Richard, Kirkham, Alex, Oldroyd, Robert, Ghei, Maneesh, Persad, Raj, Punwani, Shonit, Rosario, Derek, Shergill, Iqbal, Winkler, Mathias, Ahmed, Hashim U., Emberton, Mark, and Whitaker, Hayley C.

Published
2020
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24. Evaluation of Outcomes following Focal Ablative Therapy for Treatment of Localised Clinically Significant Prostate Cancer in Patients >70 Years: A Multi-institute, Multi-energy 15-year Experience.

Author

Habashy, David, primary, Reddy, Deepika, additional, Peters, Max, additional, Shah, Taimur T., additional, van Son, Marieke, additional, van Rossum, Peter, additional, Tanaka, Mariana Bertoncelli, additional, Cullen, Emma, additional, Engle, Ryan, additional, Stuart, McCracken, additional, Greene, Damian, additional, Hindley, Richard G., additional, Emara, Amr, additional, Nigam, Raj, additional, Orczyk, Clement, additional, Shergill, Iqbal, additional, Persad, Raj, additional, Virdi, Jaspal, additional, Moore, Caroline M., additional, Arya, Manit, additional, Winkler, Mathias, additional, Emberton, Mark, additional, Ahmed, Hashim U., additional, and Dudderidge, Tim, additional

Published
2023
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25. MP73-08 FOCAL ABLATIVE SALVAGE THERAPY FOR RADIO-RECURRENT PROSTATE CANCER: A 10 YEAR EXPERIENCE OF ONCOLOGICAL AND SAFETY OUTCOMES IN 276 PATIENTS

Author

Reddy, Deepika, primary, Shah, Taimur, additional, Cullen, Emma, additional, Tanaka, Mariana Bertoncelli, additional, Dudderidge, Tim, additional, McCracken, Stuart, additional, Nigam, Raj, additional, Virdi, Jaspal, additional, Shergill, Iqbal, additional, Orczyk, Clement, additional, Arya, Manit, additional, Moore, Caroline, additional, Emberton, Mark, additional, and Ahmed, Hashim, additional

Published
2023
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26. MP73-11 MEDIUM TERM OUTCOMES FOLLOWING PRIMARY FOCAL CRYOTHERAPY FOR LOCALISED PROSTATE CANCER IN 323 PATIENTS, A MULTI-INSTITUTIONAL OBSERVATIONAL STUDY OVER 10 YEARS

Author

Reddy, Deepika, primary, Peters, Max, additional, Van Son, Marieke, additional, Tanaka, Mariana Bertoncelli, additional, Huber, Philipp, additional, Lomas, Derek, additional, Rakauskas, Arnas, additional, Miah, Saiful, additional, Eldred-Evans, David, additional, Cullen, Emma, additional, Dudderidge, Tim, additional, McCracken, Stuart, additional, Greene, Damian, additional, Nigam, Raj, additional, McCartan, Neil, additional, Valerio, Massimo, additional, Orczyk, Clement, additional, Virdi, Jaspal, additional, Arya, Manit, additional, Shah, Taimur, additional, and Ahmed, Hashim, additional

Published
2023
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27. MP73-04 EXTERNAL VALIDATION OF A RISK SCORE PREDICTING FAILURE AFTER SALVAGE FOCAL THERAPY FOR LOCALIZED RADIORECURRENT PROSTATE CANCER: AN ANALYSIS FROM THE FOCAL RECURRENT ASSESSMENT AND SALVAGE TREATMENT (FORECAST) TRIAL

Author

Light, Alexander, primary, Peters, Max, additional, Kanthabalan, Abi, additional, Pavlou, Menelaos, additional, Omar, Rumana, additional, Adeleke, Sola, additional, Giganti, Francesco, additional, Brew-Graves, Chris, additional, Emara, Amr, additional, Haroon, Athar, additional, Latifoltojar, Arash, additional, Sidhu, Harbir, additional, Freeman, Alex, additional, Orczyk, Clement, additional, Nikapota, Ashok, additional, Dudderidge, Tim, additional, Hindley, Richard G., additional, Payne, Heather, additional, Mitra, Anita, additional, Bomanji, Jamshed, additional, Winkler, Mathias, additional, Horan, Gail, additional, Punwani, Shonit, additional, Ahmed, Hashim U., additional, and Shah, Taimur T., additional

Published
2023
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28. LBA03-07 IMPERIAL PROSTATE-4 COMPARATIVE HEALTHCARE RESEARCH OUTCOMES OF NOVEL SURGERY IN PROSTATE CANCER (IP4-CHRONOS): EARLY FEASIBILITY, SAFETY AND FUNCTIONAL OUTCOMES FROM A PILOT RCT

Author

Reddy, Deepika, primary, Dudderidge, Tim, additional, McCracken, Stuart, additional, Arya, Manit, additional, Nohpal de la Rosa, Consuelo, additional, Fiorentino, Francesca, additional, Day, Emily, additional, Prevost, Andrew, additional, Emberton, Mark, additional, Staffurth, John, additional, Sandhu, Sarbjinder, additional, Hindley, Richard, additional, Arumainayagam, Nimalan, additional, Sydes, Matthew, additional, Khoo, Vincent, additional, Winkler, Mathias, additional, Shah, Taimur, additional, and Ahmed, Hashim, additional

Published
2023
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29. MP44-02 SYSTEMATIC AND MRI-TARGETED BIOPSY STRATEGIES FOR THE DETECTION OF RADIORECURRENT PROSTATE CANCER: AN ANALYSIS FROM THE FOCAL RECURRENT ASSESSMENT AND SALVAGE TREATMENT (FORECAST) TRIAL

Author

Light, Alexander, primary, Kanthabalan, Abi, additional, Pavlou, Menelaos, additional, Omar, Rumana, additional, Adeleke, Sola, additional, Giganti, Francesco, additional, Brew-Graves, Chris, additional, Emara, Amr, additional, Haroon, Athar, additional, Latifoltojar, Arash, additional, Sidhu, Harbir, additional, Freeman, Alex, additional, Nikapota, Ashok, additional, Dudderidge, Tim, additional, Hindley, Richard G., additional, Payne, Heather, additional, Mitra, Anita, additional, Bomanji, Jamshed, additional, Winkler, Mathias, additional, Horan, Gail, additional, Punwani, Shonit, additional, Ahmed, Hashim U., additional, and Shah, Taimur T., additional

Published
2023
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30. MP44-06 TUMOR CHARACTERISTICS OF MULTIPARAMETRIC MRI-DETECTED AND -UNDETECTED LESIONS IN PATIENTS WITH SUSPECTED RADIORECURRENT PROSTATE CANCER: AN ANALYSIS FROM THE FOCAL RECURRENT ASSESSMENT AND SALVAGE TREATMENT (FORECAST) TRIAL

Author

Light, Alexander, primary, Kanthabalan, Abi, additional, Pavlou, Menelaos, additional, Omar, Rumana, additional, Adeleke, Sola, additional, Giganti, Francesco, additional, Brew-Graves, Chris, additional, Emara, Amr, additional, Haroon, Athar, additional, Latifoltojar, Arash, additional, Sidhu, Harbir, additional, Freeman, Alex, additional, Orczyk, Clement, additional, Nikapota, Ashok, additional, Dudderidge, Tim, additional, Hindley, Richard G., additional, Payne, Heather, additional, Mitra, Anita, additional, Bomanji, Jamshed, additional, Winkler, Mathias, additional, Horan, Gail, additional, Punwani, Shonit, additional, Ahmed, Hashim U., additional, and Shah, Taimur T., additional

Published
2023
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31. External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

Author

MS Radiotherapie, Light, Alexander, Peters, Max, Reddy, Deepika, Kanthabalan, Abi, Otieno, Marjorie, Pavlou, Menelaos, Omar, Rumana, Adeleke, Sola, Giganti, Francesco, Brew-Graves, Chris, Williams, Norman R, Emara, Amr, Haroon, Athar, Latifoltojar, Arash, Sidhu, Harbir, Freeman, Alex, Orczyk, Clement, Nikapota, Ashok, Dudderidge, Tim, Hindley, Richard G, Virdi, Jaspal, Arya, Manit, Payne, Heather, Mitra, Anita V, Bomanji, Jamshed, Winkler, Mathias, Horan, Gail, Moore, Caroline, Emberton, Mark, Punwani, Shonit, Ahmed, Hashim U, Shah, Taimur T, MS Radiotherapie, Light, Alexander, Peters, Max, Reddy, Deepika, Kanthabalan, Abi, Otieno, Marjorie, Pavlou, Menelaos, Omar, Rumana, Adeleke, Sola, Giganti, Francesco, Brew-Graves, Chris, Williams, Norman R, Emara, Amr, Haroon, Athar, Latifoltojar, Arash, Sidhu, Harbir, Freeman, Alex, Orczyk, Clement, Nikapota, Ashok, Dudderidge, Tim, Hindley, Richard G, Virdi, Jaspal, Arya, Manit, Payne, Heather, Mitra, Anita V, Bomanji, Jamshed, Winkler, Mathias, Horan, Gail, Moore, Caroline, Emberton, Mark, Punwani, Shonit, Ahmed, Hashim U, and Shah, Taimur T

Published
2023

32. Evaluation of Outcomes Following Focal Ablative Therapy for Treatment of Localized Clinically Significant Prostate Cancer in Patients >70 Years: A Multi-institute, Multi-energy 15-Year Experience

Author

MS Radiotherapie, Onderzoek Radiotherapie, Cancer, Habashy, David, Reddy, Deepika, Peters, Max, Shah, Taimur T, van Son, Marieke, van Rossum, Peter, Tanaka, Mariana Bertoncelli, Cullen, Emma, Engle, Ryan, McCracken, Stuart, Greene, Damian, Hindley, Richard G, Emara, Amr, Nigam, Raj, Orczyk, Clement, Shergill, Iqbal, Persad, Raj, Virdi, Jaspal, Moore, Caroline M, Arya, Manit, Winkler, Mathias, Emberton, Mark, Ahmed, Hashim U, Dudderidge, Tim, MS Radiotherapie, Onderzoek Radiotherapie, Cancer, Habashy, David, Reddy, Deepika, Peters, Max, Shah, Taimur T, van Son, Marieke, van Rossum, Peter, Tanaka, Mariana Bertoncelli, Cullen, Emma, Engle, Ryan, McCracken, Stuart, Greene, Damian, Hindley, Richard G, Emara, Amr, Nigam, Raj, Orczyk, Clement, Shergill, Iqbal, Persad, Raj, Virdi, Jaspal, Moore, Caroline M, Arya, Manit, Winkler, Mathias, Emberton, Mark, Ahmed, Hashim U, and Dudderidge, Tim

Published
2023

33. Corrigendum to “Magnetic Resonance Imaging and targeted biopsies compared to transperineal mapping biopsies prior to salvage focal therapy/ablation in localised and metastatic recurrent prostate cancer after radiotherapy. Primary Outcomes from the FORECAST Trial” [Eur Urol 2022;81(6):598–605]

Author

Shah, Taimur T., primary, Kanthabalan, Abi, additional, Otieno, Marjorie, additional, Pavlou, Menelaos, additional, Omar, Rumana, additional, Adeleke, Sola, additional, Giganti, Francesco, additional, Brew-Graves, Chris, additional, Williams, Norman R., additional, Grierson, Jack, additional, Miah, Haroon, additional, Emara, Amr, additional, Haroon, Athar, additional, Latifoltojar, Arash, additional, Sidhu, Harbir, additional, Clemente, Joey, additional, Freeman, Alex, additional, Orczyk, Clement, additional, Nikapota, Ashok, additional, Dudderidge, Tim, additional, Hindley, Richard G., additional, Virdi, Jaspal, additional, Arya, Manit, additional, Payne, Heather, additional, Mitra, Anita, additional, Bomanji, Jamshed, additional, Winkler, Mathias, additional, Horan, Gail, additional, Moore, Caroline M., additional, Emberton, Mark, additional, Punwani, Shonit, additional, and Ahmed, Hashim U., additional

Published
2023
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34. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Author

Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Al-Shahrour, Fatima, Bailey, Peter J, Biankin, Andrew V, Boutros, Paul C, Campbell, Peter J, Chang, David K, Cooke, Susanna L, Deshpande, Vikram, Faltas, Bishoy M, Faquin, William C, Garraway, Levi, Getz, Gad, Grimmond, Sean M, Haider, Syed, Hoadley, Katherine A, Kaiser, Vera B, Kato, Mamoru, Kübler, Kirsten, Lazar, Alexander J, Li, Constance H, Louis, David N, Margolin, Adam, Martin, Sancha, Nahal-Bose, Hardeep K, Nielsen, G Petur, Nik-Zainal, Serena, Omberg, Larsson, P’ng, Christine, Perry, Marc D, Rheinbay, Esther, Rubin, Mark A, Semple, Colin A, Sgroi, Dennis C, Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D, Stobbe, Miranda D, Sun, Ren X, Thai, Kevin, Wright, Derek W, Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Morris, Quaid D, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlevaro-Fita, Joana, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chakravarty, Dimple, Chalmers, Don, Chan, Calvin Wing Yiu, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Ken, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Jung Kyoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshwar, Amit G, Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C, Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Fan, Daiming, Fan, Yu, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Feuerbach, Lars, Field, Matthew A, Fink, J Lynn, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Fonseca, Nuno A, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Frigola, Joan, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gallinger, Steven, Gambacorti-Passerini, Carlo, Gao, Jianjiong, Gao, Shengjie, Garred, Øystein, Garrison, Erik, Garsed, Dale W, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstein, Mark, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gonzalez-Perez, Abel, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Guo, Qianyun, Gupta, Manaswi, Gupta, Shailja, Gut, Ivo G, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haan, David, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Hamilton, Mark P, Han, Leng, Hanna, George B, Hansmann, Martin, Haradhvala, Nicholas J, Harismendy, Olivier, Harliwong, Ivon, Harmanci, Arif O, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hess, Julian M, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hobolth, Asger, Hodzic, Ermin, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Chen, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hornshøj, Henrik, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose MG, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Johnson, Rory, Johnson, Todd A, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, David TW, Jones, Nic, Jones, Steven JM, Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Jung, Jongsun, Juul, Malene, Juul, Randi Istrup, Juul, Sissel, Jäger, Natalie, Kabbe, Rolf, Kahles, Andre, Kahraman, Abdullah, Kakavand, Hojabr, Kalimuthu, Sangeetha, von Kalle, Christof, Kang, Koo Jeong, Karaszi, Katalin, Karlan, Beth, Karlić, Rosa, Karsch, Dennis, Kasaian, Katayoon, Kassahn, Karin S, Katai, Hitoshi, Katoh, Hiroto, Kawakami, Yoshiiku, Kay, Jonathan D, Kazakoff, Stephen H, Kazanov, Marat D, Keays, Maria, Kebebew, Electron, Kefford, Richard F, Kellis, Manolis, Kench, James G, Kennedy, Catherine J, Kerssemakers, Jules NA, Khoo, David, Khoo, Vincent, Khuntikeo, Narong, Khurana, Ekta, Kilpinen, Helena, Kim, Hark Kyun, Kim, Hyung-Lae, Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jaegil, Kim, Jihoon, Kim, Jong K, Kim, Youngwook, King, Tari A, Klapper, Wolfram, Kleinheinz, Kortine, Klimczak, Leszek J, Knappskog, Stian, Kneba, Michael, Knoppers, Bartha M, Koh, Youngil, Komorowski, Jan, Komura, Daisuke, Komura, Mitsuhiro, Kong, Gu, Kool, Marcel, Korbel, Jan O, Korchina, Viktoriya, Korshunov, Andrey, Koscher, Michael, Koster, Roelof, Kote-Jarai, Zsofia, Koures, Antonios, Kovacevic, Milena, Kremeyer, Barbara, Kretzmer, Helene, Kreuz, Markus, Krishnamurthy, Savitri, Kube, Dieter, Kumar, Kiran, Kumar, Pardeep, Kumar, Sushant, Kumar, Yogesh, Kundra, Ritika, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H, Laird, Peter W, Lakhani, Sunil R, Lalansingh, Christopher M, Lalonde, Emilie, Lamaze, Fabien C, Lambert, Adam, Lander, Eric, Landgraf, Pablo, Landoni, Luca, Langerød, Anita, Lanzós, Andrés, Larsimont, Denis, Larsson, Erik, Lathrop, Mark, Lau, Loretta MS, Lawerenz, Chris, Lawlor, Rita T, Lawrence, Michael S, Lazic, Ana Mijalkovic, Le, Xuan, Lee, Darlene, Lee, Donghoon, Lee, Eunjung Alice, Lee, Hee Jin, Lee, Jake June-Koo, Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael, Lee-Six, Henry, Lehmann, Kjong-Van, Lehrach, Hans, Lenze, Dido, Leonard, Conrad R, Leongamornlert, Daniel A, Leshchiner, Ignaty, Letourneau, Louis, Letunic, Ivica, Levine, Douglas A, Lewis, Lora, Ley, Tim, Li, Chang, Li, Haiyan Irene, Li, Jun, Li, Lin, Li, Shantao, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Li, Yilong, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Lin, Ziao, Linehan, WM, Lingjærde, Ole Christian, Liu, Dongbing, Liu, Eric Minwei, Liu, Fei-Fei Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, Livitz, Dimitri, Livni, Naomi, Lochovsky, Lucas, Loeffler, Markus, Long, Georgina V, Lopez-Guillermo, Armando, Lou, Shaoke, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lynch, Andy G, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, Macintyre, Geoff, Madsen, Tobias, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchal, Kathleen, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowetz, Florian, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin-Subero, Jose I, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, Mashl, R Jay, Massie, Charlie E, Matthew, Thomas J, Matthews, Lucy, Mayer, Erik, Mayes, Simon, Mayo, Michael, Mbabaali, Faridah, McCune, Karen, McDermott, Ultan, McGillivray, Patrick D, McLellan, Michael D, McPherson, John D, McPherson, John R, McPherson, Treasa A, Meier, Samuel R, Meng, Alice, Meng, Shaowu, Menzies, Andrew, Merrett, Neil D, Merson, Sue, Meyerson, Matthew, Meyerson, William, Mieczkowski, Piotr A, Mihaiescu, George L, Mijalkovic, Sanja, Mikkelsen, Tom, Milella, Michele, Mileshkin, Linda, Miller, Christopher A, Miller, David K, Miller, Jessica K, Mills, Gordon B, Milovanovic, Ana, Minner, Sarah, Miotto, Marco, Arnau, Gisela Mir, Mirabello, Lisa, Mitchell, Chris, Mitchell, Thomas J, Miyano, Satoru, Miyoshi, Naoki, Mizuno, Shinichi, Molnár-Gábor, Fruzsina, Moore, Malcolm J, Moore, Richard A, Morganella, Sandro, Morrison, Carl, Mose, Lisle E, Moser, Catherine D, Muiños, Ferran, Mularoni, Loris, Mungall, Andrew J, Mungall, 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Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian

Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.

Published
2023
Full Text
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35. Combined burden and functional impact tests for cancer driver discovery using DriverPower

Author

Shuai, Shimin, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Barenboim, Jonathan, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reimand, Jüri, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, Uusküla-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven PC, Wadelius, 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Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.

Published
2023
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36. Integrative pathway enrichment analysis of multivariate omics data

Author

Paczkowska, Marta, Barenboim, Jonathan, Sintupisut, Nardnisa, Fox, Natalie S, Zhu, Helen, Abd-Rabbo, Diala, Mee, Miles W, Boutros, Paul C, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Gonzalez-Perez, Abel, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pich, Oriol, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sabarinathan, Radhakrishnan, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, 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Vijver, Marc J, and Veer, L van’t

Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.

Published
2023
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37. Pathway and network analysis of more than 2500 whole cancer genomes

Author

Reyna, Matthew A, Haan, David, Paczkowska, Marta, Verbeke, Lieven PC, Vazquez, Miguel, Kahraman, Abdullah, Pulido-Tamayo, Sergio, Barenboim, Jonathan, Wadi, Lina, Dhingra, Priyanka, Shrestha, Raunak, Getz, Gad, Lawrence, Michael S, Pedersen, Jakob Skou, Rubin, Mark A, Wheeler, David A, Brunak, Søren, Izarzugaza, Jose MG, Khurana, Ekta, Marchal, Kathleen, von Mering, Christian, Sahinalp, S Cenk, Valencia, Alfonso, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Busanovich, John, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Guo, Qianyun, Gut, Ivo G, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kellis, Manolis, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pons, Tirso, Reyes-Salazar, Iker, Rheinbay, Esther, Rubio-Perez, Carlota, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, 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Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.

Published
2023
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38. Divergent mutational processes distinguish hypoxic and normoxic tumours

Author

Bhandari, Vinayak, Li, Constance H, Bristow, Robert G, Boutros, Paul C, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, 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Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.

Published
2023
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39. Genomic footprints of activated telomere maintenance mechanisms in cancer

Author

Sieverling, Lina, Hong, Chen, Koser, Sandra D, Ginsbach, Philip, Kleinheinz, Kortine, Hutter, Barbara, Braun, Delia M, Cortés-Ciriano, Isidro, Xi, Ruibin, Kabbe, Rolf, Park, Peter J, Eils, Roland, Schlesner, Matthias, Akdemir, Kadir C, Alvarez, Eva G, Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C, Bowtell, David DL, Brors, Benedikt, Burns, Kathleen H, Campbell, Peter J, Chan, Kin, Chen, Ken, Dueso-Barroso, Ana, Dunford, Andrew J, Edwards, Paul A, Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W, Gerstein, Mark, Gordenin, Dmitry A, Haan, David, Haber, James E, Hess, Julian M, Imielinski, Marcin, Jones, David TW, Ju, Young Seok, Kazanov, Marat D, Klimczak, Leszek J, Koh, Youngil, Korbel, Jan O, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Li, Yilong, Lynch, Andy G, Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Meyerson, Matthew, Miyano, Satoru, Nakagawa, 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Michael, Koster, Roelof, Kote-Jarai, Zsofia, Koures, Antonios, Kovacevic, Milena, Kremeyer, Barbara, Kretzmer, Helene, Kreuz, Markus, Krishnamurthy, Savitri, Kube, Dieter, Kumar, Pardeep, Kumar, Sushant, Kumar, Yogesh, Kundra, Ritika, Kübler, Kirsten, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H, Laird, Peter W, Lakhani, Sunil R, Lalansingh, Christopher M, Lalonde, Emilie, Lamaze, Fabien C, Lambert, Adam, Lander, Eric, Landgraf, Pablo, Landoni, Luca, Langerød, Anita, Lanzós, Andrés, Larsimont, Denis, Larsson, Erik, Lathrop, Mark, Lau, Loretta MS, Lawerenz, Chris, Lawlor, Rita T, Lawrence, Michael S, Lazar, Alexander J, Lazic, Ana Mijalkovic, Le, Xuan, Lee, Darlene, Lee, Donghoon, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael, Lee-Six, Henry, Lehmann, Kjong-Van, Lehrach, Hans, Lenze, Dido, Leonard, Conrad R, Leongamornlert, Daniel A, Leshchiner, Ignaty, Letourneau, Louis, Letunic, Ivica, Levine, Douglas A, Lewis, Lora, Ley, Tim, Li, Chang, Li, Constance H, Li, Haiyan Irene, Li, Jun, Li, Lin, Li, Shantao, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Lin, Ziao, Linehan, WM, Lingjærde, Ole Christian, Liu, Dongbing, Liu, Eric Minwei, Liu, Fei-Fei Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, Livitz, Dimitri, Livni, Naomi, Lochovsky, Lucas, Loeffler, Markus, Long, Georgina V, Lopez-Guillermo, Armando, Lou, Shaoke, Louis, David N, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, Madsen, Tobias, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchal, Kathleen, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowski, Julia, 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Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, Prinz, Manuel, Pritchard, Antonia L, Prokopec, Stephenie D, Provenzano, Elena, Puente, Xose S, Puig, Sonia, Pulido-Tamayo, Sergio, Pupo, Gulietta M, Purdie, Colin A, Quinn, Michael C, Rabionet, Raquel, Rader, Janet S, Radlwimmer, Bernhard, Radovic, Petar, Raeder, Benjamin, Raine, Keiran M, Ramakrishna, Manasa, Ramakrishnan, Kamna, Ramalingam, Suresh, Raphael, Benjamin J, Rathmell, W Kimryn, Rausch, Tobias, Reifenberger, Guido, Reimand, Jüri, Reis-Filho, Jorge, Reuter, Victor, Reyes-Salazar, Iker, Reyna, Matthew A, Reynolds, Sheila M, Rheinbay, Esther, Riazalhosseini, Yasser, Richardson, Andrea L, Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Roach, Jeffrey, Roberts, Lewis R, Robertson, A Gordon, Robertson, Alan J, Rodriguez, Javier Bartolomé, Rodríguez-González, F Germán, Roehrl, Michael HA, Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C, Rosenwald, Andreas, Rowe, Edward W, Royo, Romina, Rozen, Steven G, Rubanova, Yulia, Rubin, Mark A, Rubio-Perez, Carlota, Rudneva, Vasilisa A, Rusev, Borislav C, Ruzzenente, Andrea, Rätsch, Gunnar, Sabarinathan, Radhakrishnan, Sabelnykova, Veronica Y, Sadeghi, Sara, Sahinalp, S Cenk, Saini, Natalie, Saito-Adachi, Mihoko, Saksena, Gordon, Salcedo, Adriana, Salgado, Roberto, Salichos, Leonidas, Sallari, Richard, Saller, Charles, Salvia, Roberto, Sam, Michelle, Samra, Jaswinder S, Sanchez-Vega, Francisco, Sander, Chris, Sanders, Grant, Sarin, Rajiv, Sarrafi, Iman, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn PM, Scardoni, Maria, Scarlett, Christopher J, Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E, Schilhabel, Markus B, Schlomm, Thorsten, Schmidt, Heather K, Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schwarz, Roland F, Scolyer, Richard A, Scott, David, Seethala, Raja, Segre, Ayellet V, Selander, Iris, Semple, Colin A, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shapira, Ofer, Shelton, Troy, Shen, Ciyue, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shrestha, Raunak, Shringarpure, Suyash S, Shriver, Craig, Shuai, Shimin, Siebert, Reiner, Sieuwerts, Anieta M, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sinnott-Armstrong, Nasa, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stein, Lincoln D, Stenhouse, Alasdair, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stuart, Joshua M, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tamborero, David, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tiao, Grace, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, Tsunoda, Tatsuhiko, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Umer, Husen M, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Uusküla-Reimand, Liis, Valencia, Alfonso, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vazquez, Miguel, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Verbeke, Lieven PC, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M, Wadelius, Claes, Wadi, Lina, Wagener, Rabea, Wang, Jian, Wang, Jiayin, Wang, Linghua, Wang, Qi, Wang, Wenyi, Wang, Yumeng, Wang, Zhining, Waring, Paul M, Warnatz, Hans-Jörg, Warrell, Jonathan, Warren, Anne Y, Waszak, Sebastian M, Wedge, David C, Weichenhan, Dieter, Weinberger, Paul, Weinstein, John N, Weisenberger, Daniel J, Welch, Ian, Wendl, Michael C, Werner, Johannes, Whalley, Justin P, Wheeler, David A, Whitaker, Hayley C, Wigle, Dennis, Wilkerson, Matthew D, Williams, Ashley, Wilmott, James S, Wilson, Gavin W, Wilson, Julie M, Wilson, Richard K, Winterhoff, Boris, Wintersinger, Jeffrey A, Wiznerowicz, Maciej, Wolf, Stephan, Wong, Bernice H, Wong, Tina, Wong, Winghing, Woo, Youngchoon, Wood, Scott, Wouters, Bradly G, Wright, Adam J, Wright, Derek W, Wright, Mark H, Wu, Chin-Lee, Wu, Dai-Ying, Wu, Guanming, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Zhenggang, Xi, Liu, Xia, Tian, Xiang, Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Junjun, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian

Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.

Published
2023
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40. The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates

Author

Buhigas, Claudia, Warren, Anne Y., Leung, Wing-Kit, Whitaker, Hayley C., Luxton, Hayley J., Hawkins, Steve, Kay, Jonathan, Butler, Adam, Xu, Yaobo, Woodcock, Dan J., Merson, Sue, Frame, Fiona M., Sahli, Atef, Abascal, Federico, Gihawi, Abraham, Lambert, Adam, Thompson, Alan, Futreal, Andrew, Menzies, Andrew, Baddage, Anne, Ng, Anthony, Sahil, Atef, Kremeyer, Barbara, Al-Lazikani, Bissan, Massie, Charlie, Greenman, Christopher, Ogden, Christopher, Verrill, Clare, Fisher, Cyril, Berney, Dan, Burns, Dan, Leongamornlert, Daniel, Jones, David, Nicol, David, Wedge, David C., Cahill, Declan, Easton, Douglas, Rowe, Edward, Riabchenko, Ekaterina, Bancroft, Elizabeth, Mayer, Erik, Anokian, Ezequiel, Hamdy, Freddie, Park, Gahee, Pelvender, Gill, Leeman, Gregory, Gundem, Gunes, Zhang, Hongwei, Mills, Ian G., Zhang, Jingjing, Teague, Jon, Zamora, Jorge, Karaszi, Katalin, Raine, Kieran, Matthews, Lucy, Stebbings, Lucy, Alexandrov, Ludmil B., Marsden, Luke, Ahmed, Mahbubl, Nykter, Matti, Ghori, Mohammed, Livni, Naomi, Dennis, Nening, Van As, Nicholas, Camacho, Niedzica, Shah, Nimish, Kumar, Pardeep, Van Loo, Peter, Lach, Radoslaw, Edwards, Sandra, Pita, Sara, Field, Sarah J., Thomas, Sarah, Tavaré, Simon, Scalabrino, Stefania, Hazell, Steven, McLaren, Stuart, Visakorpi, Tapio, Mitchell, Thomas J., Dudderidge, Tim, Dadaev, Tokhir, McDermott, Ultan, Bo, Valeria, Haberland, Valeriia, Gnanapragasam, Vincent, Khoo, Vincent, Howat, William, Jie-Lu, Yong, Yu, Yongwei, Kote-Jarai, Zsofia, Martincorena, Iñigo, Bova, G. Steven, Foster, Christopher S., Campbell, Peter, Maitland, Norman J., Neal, David E., Massie, Charlie E., Lynch, Andy G., Eeles, Rosalind A., Cooper, Colin S., Brewer, Daniel S., Group, CRUK-ICGC Prostate Cancer, University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. St Andrews Bioinformatics Unit, University of St Andrews. Cellular Medicine Division, Tampere University, BioMediTech, Group, CRUK-ICGC Prostate Cancer, Apollo - University of Cambridge Repository, Lynch, Andy G [0000-0002-7876-7338], and Brewer, Daniel S [0000-0003-4753-9794]

Subjects
Male, Cancer Research, Prostatic Hyperplasia, Normal tissue, Mutational signatures, QH426 Genetics, Clonal expansions, Field effect, RC0254, Ecology,Evolution & Ethology, SDG 3 - Good Health and Well-being, NCAD, Humans, QH426, Computational & Systems Biology, MCC, Human Biology & Physiology, Prostate cancer, Benign prostatic hyperplasia, Nucleotides, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Research, Prostate, Prostatic Neoplasms, DAS, Genomics, Tumour Biology, Clone Cells, Oncology, Molecular Medicine, 3111 Biomedicine, Genetics & Genomics
Abstract

Background Up to 80% of cases of prostate cancer present with multifocal independent tumour lesions leading to the concept of a field effect present in the normal prostate predisposing to cancer development. In the present study we applied Whole Genome DNA Sequencing (WGS) to a group of morphologically normal tissue (n = 51), including benign prostatic hyperplasia (BPH) and non-BPH samples, from men with and men without prostate cancer. We assess whether the observed genetic changes in morphologically normal tissue are linked to the development of cancer in the prostate. Results Single nucleotide variants (P = 7.0 × 10–03, Wilcoxon rank sum test) and small insertions and deletions (indels, P = 8.7 × 10–06) were significantly higher in morphologically normal samples, including BPH, from men with prostate cancer compared to those without. The presence of subclonal expansions under selective pressure, supported by a high level of mutations, were significantly associated with samples from men with prostate cancer (P = 0.035, Fisher exact test). The clonal cell fraction of normal clones was always higher than the proportion of the prostate estimated as epithelial (P = 5.94 × 10–05, paired Wilcoxon signed rank test) which, along with analysis of primary fibroblasts prepared from BPH specimens, suggests a stromal origin. Constructed phylogenies revealed lineages associated with benign tissue that were completely distinct from adjacent tumour clones, but a common lineage between BPH and non-BPH morphologically normal tissues was often observed. Compared to tumours, normal samples have significantly less single nucleotide variants (P = 3.72 × 10–09, paired Wilcoxon signed rank test), have very few rearrangements and a complete lack of copy number alterations. Conclusions Cells within regions of morphologically normal tissue (both BPH and non-BPH) can expand under selective pressure by mechanisms that are distinct from those occurring in adjacent cancer, but that are allied to the presence of cancer. Expansions, which are probably stromal in origin, are characterised by lack of recurrent driver mutations, by almost complete absence of structural variants/copy number alterations, and mutational processes similar to malignant tissue. Our findings have implications for treatment (focal therapy) and early detection approaches.

Published
2022

41. Comparative healthcare research outcomes of novel Surgery in prostate cancer (IP4-CHRONOS): Pilot RCT assessing feasibility of randomization for focal therapy in localized prostate cancer.

Author

Reddy, Deepika, primary, Dudderidge, Tim, additional, Shah, Taimur, additional, McCracken, Stuart, additional, Arya, Manit, additional, Fiorentino, Francesca, additional, Day, Emily, additional, Prevost, Andrew, additional, Emberton, Mark, additional, Staffurth, John, additional, Sandhu, Sarbjinder, additional, Hindley, Richard, additional, Arumainayagam, Nim, additional, Sydes, Matthew R., additional, Khoo, Vincent, additional, Winkler, Mathias, additional, and Ahmed, Hashim Uddin, additional

Published
2022
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42. MP55-01 CANCER CONTROL OUTCOMES FOLLOWING FOCAL THERAPY USING HIFU IN 1,379 MEN WITH NON-METASTATIC PROSTATE CANCER: A MULTI-INSTITUTE 15-YEAR EXPERIENCE

Author

Reddy, Deepika, primary, Peters, Max, additional, Shah, Taimur, additional, van Son, Marieke, additional, Bertoncelli, Mariana Tanaka, additional, Huber, Philipp, additional, Lomas, Derek, additional, Rakauskas, Arnas, additional, Miah, Saiful, additional, Eldred-Evans, David, additional, Guillaumier, Stephanie, additional, Hosking-Jervis, Feargus, additional, Engle, Ryan, additional, Dudderidge, Tim, additional, Hindley, Richard, additional, Emara, Amr, additional, Nigam, Raj, additional, McCartan, Neil, additional, Valerio, Massimo, additional, Afzal, Naveed, additional, Lewi, Henry, additional, Orczyk, Clement, additional, Ogden, Chris, additional, Shergill, Iqbal, additional, Persad, Raj, additional, Virdi, Jaspal, additional, Moore, Caroline, additional, Arya, Manit, additional, Winkler, Mathias, additional, Emberton, Mark, additional, and Ahmed, Hashim, additional

Published
2022
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43. MP55-06 FOCAL ABLATIVE SALVAGE THERAPY FOR RADIO-RECURRENT PROSTATE CANCER: 6 YEAR ONCOLOGICAL AND SAFETY OUTCOMES

Author

Reddy, Deepika, primary, Peters, Max, additional, Shah, Taimur, additional, van Son, Marieke, additional, Bertoncelli, Mariana Tanaka, additional, Huber, Philipp, additional, Lomas, Derek, additional, Rakauskas, Arnas, additional, Miah, Saiful, additional, Eldred-Evans, David, additional, Guillaumier, Stephanie, additional, Hosking-Jervis, Feargus, additional, Engle, Ryan, additional, Dudderidge, Tim, additional, Hindley, Richard, additional, Emara, Amr, additional, Nigam, Raj, additional, McCartan, Neil, additional, Valerio, Massimo, additional, Afzal, Naveed, additional, Lewi, Henry, additional, Orczyk, Clement, additional, Ogden, Chris, additional, Shergill, Iqbal, additional, Persad, Raj, additional, Virdi, Jaspal, additional, McCracken, Stuart, additional, Greene, Damian, additional, Moore, Caroline, additional, Arya, Manit, additional, Winkler, Mathias, additional, Emberton, Mark, additional, and Ahmed, Hashim, additional

Published
2022
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44. Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience

Author

Arts-assistenten Radiotherapie, Onderzoek Radiotherapie, Reddy, Deepika, Peters, Max, Shah, Taimur T, van Son, Marieke, Tanaka, Mariana Bertoncelli, Huber, Philipp M, Lomas, Derek, Rakauskas, Arnas, Miah, Saiful, Eldred-Evans, David, Guillaumier, Stephanie, Hosking-Jervis, Feargus, Engle, Ryan, Dudderidge, Tim, Hindley, Richard G, Emara, Amr, Nigam, Raj, McCartan, Neil, Valerio, Massimo, Afzal, Naveed, Lewi, Henry, Orczyk, Clement, Ogden, Chris, Shergill, Iqbal, Persad, Raj, Virdi, Jaspal, Moore, Caroline M, Arya, Manit, Winkler, Mathias, Emberton, Mark, Ahmed, Hashim U, Arts-assistenten Radiotherapie, Onderzoek Radiotherapie, Reddy, Deepika, Peters, Max, Shah, Taimur T, van Son, Marieke, Tanaka, Mariana Bertoncelli, Huber, Philipp M, Lomas, Derek, Rakauskas, Arnas, Miah, Saiful, Eldred-Evans, David, Guillaumier, Stephanie, Hosking-Jervis, Feargus, Engle, Ryan, Dudderidge, Tim, Hindley, Richard G, Emara, Amr, Nigam, Raj, McCartan, Neil, Valerio, Massimo, Afzal, Naveed, Lewi, Henry, Orczyk, Clement, Ogden, Chris, Shergill, Iqbal, Persad, Raj, Virdi, Jaspal, Moore, Caroline M, Arya, Manit, Winkler, Mathias, Emberton, Mark, and Ahmed, Hashim U

Published
2022

46. A systematic review of patients' values, preferences, and expectations for the treatment of metastatic prostate cancer

Author

Connor, Martin J, Genie, Mesfin G, Burns, David, Bass, Edward J, Gonzalez, Michael, Sarwar, Naveed, Falconer, Alison, Mangar, Stephen, Dudderidge, Tim, Khoo, Vincent, Winkler, Mathias, Ahmed, Hashim U, and Watson, Verity

Abstract

Context: advances in systemic agents have increased overall survival for men diagnosed with metastatic prostate cancer. Additional cytoreductive prostate treatments and metastasis-directed therapies are under evaluation. These confer toxicity but may offer incremental survival benefits. Thus, an understanding of patients' values and treatment preferences is important for counselling, decision-making, and guideline development.Objective: to perform a systematic review of patients' values, preferences, and expectations regarding treatment of metastatic prostate cancer.Evidence acquisition: the MEDLINE, Embase, and CINAHL databases were systematically searched for qualitative and preference elucidation studies reporting on patients' preferences for treatment of metastatic prostate cancer. Certainty of evidence was assessed using Grading of Recommendation, Assessment, Development and Evaluation (GRADE) or GRADE Confidence in the Evidence from Reviews of Qualitative Research (CERQual). The protocol was registered on PROSPERO as CRD42020201420.Evidence synthesis: a total of 1491 participants from 15 studies met the prespecified eligibility for inclusion. The study designs included were discrete choice experiments (n = 5), mixed methods (n = 3), and qualitative methods (n = 7). Disease states reported per study were: metastatic castration-resistant prostate cancer in nine studies (60.0%), metastatic hormone-sensitive prostate cancer in two studies (13.3%), and a mixed cohort in four studies (26.6%). In quantitative preference elicitation studies, patients consistently valued treatment effectiveness and delay in time to symptoms as the two top-ranked treatment attributes (low or very low certainty). Patients were willing to trade off treatment-related toxicity for potential oncological benefits (low certainty). In qualitative studies, thematic analysis revealed cancer progression and/or survival, pain, and fatigue as key components in treatment decisions (low or very low certainty). Patients continue to value oncological benefits in making decisions on treatments under qualitative assessment.Conclusions: there is limited understanding of how patients make treatment and trade-off decisions following a diagnosis of metastatic prostate cancer. For appropriate investment in emerging cytoreductive local tumour and metastasis-directed therapies, we should seek to better understand how this cohort weighs the oncological benefits against the risks.Patient summary: We looked at how men with advanced (metastatic) prostate cancer make treatment decisions. We found that little is known about patients' preferences for current and proposed new treatments. Further studies are required to understand how patients make decisions to help guide the integration of new treatments into the standard of care.

Published
2021

47. Metastatic prostate cancer men’s attitudes towards treatment of the local tumour and metastasis evaluative research (IP5-MATTER): protocol for a prospective, multicentre discrete choice experiment study

Author

Connor, Martin John, primary, Genie, Mesfin G, additional, Gonzalez, Michael, additional, Sarwar, Naveed, additional, Thippu Jayaprakash, Kamalram, additional, Horan, Gail, additional, Hosking-Jervis, Feargus, additional, Klimowska-Nassar, Natalia, additional, Sukumar, Johanna, additional, Pokrovska, Tzveta, additional, Basak, Dolan, additional, Robinson, Angus, additional, Beresford, Mark, additional, Rai, Bhavan, additional, Mangar, Stephen, additional, Khoo, Vincent, additional, Dudderidge, Tim, additional, Falconer, Alison, additional, Winkler, Mathias, additional, Watson, Verity, additional, and Ahmed, Hashim Uddin, additional

Published
2021
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48. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study

Author

Bancroft, Elizabeth K, primary, Page, Elizabeth C, additional, Brook, Mark N, additional, Thomas, Sarah, additional, Taylor, Natalie, additional, Pope, Jennifer, additional, McHugh, Jana, additional, Jones, Ann-Britt, additional, Karlsson, Questa, additional, Merson, Susan, additional, Ong, Kai Ren, additional, Hoffman, Jonathan, additional, Huber, Camilla, additional, Maehle, Lovise, additional, Grindedal, Eli Marie, additional, Stormorken, Astrid, additional, Evans, D Gareth, additional, Rothwell, Jeanette, additional, Lalloo, Fiona, additional, Brady, Angela F, additional, Bartlett, Marion, additional, Snape, Katie, additional, Hanson, Helen, additional, James, Paul, additional, McKinley, Joanne, additional, Mascarenhas, Lyon, additional, Syngal, Sapna, additional, Ukaegbu, Chinedu, additional, Side, Lucy, additional, Thomas, Tessy, additional, Barwell, Julian, additional, Teixeira, Manuel R, additional, Izatt, Louise, additional, Suri, Mohnish, additional, Macrae, Finlay A, additional, Poplawski, Nicola, additional, Chen-Shtoyerman, Rakefet, additional, Ahmed, Munaza, additional, Musgrave, Hannah, additional, Nicolai, Nicola, additional, Greenhalgh, Lynn, additional, Brewer, Carole, additional, Pachter, Nicholas, additional, Spigelman, Allan D, additional, Azzabi, Ashraf, additional, Helfand, Brian T, additional, Halliday, Dorothy, additional, Buys, Saundra, additional, Ramon y Cajal, Teresa, additional, Donaldson, Alan, additional, Cooney, Kathleen A, additional, Harris, Marion, additional, McGrath, John, additional, Davidson, Rosemarie, additional, Taylor, Amy, additional, Cooke, Peter, additional, Myhill, Kathryn, additional, Hogben, Matthew, additional, Aaronson, Neil K, additional, Ardern-Jones, Audrey, additional, Bangma, Chris H, additional, Castro, Elena, additional, Dearnaley, David, additional, Dias, Alexander, additional, Dudderidge, Tim, additional, Eccles, Diana M, additional, Green, Kate, additional, Eyfjord, Jorunn, additional, Falconer, Alison, additional, Foster, Christopher S, additional, Gronberg, Henrik, additional, Hamdy, Freddie C, additional, Johannsson, Oskar, additional, Khoo, Vincent, additional, Lilja, Hans, additional, Lindeman, Geoffrey J, additional, Lubinski, Jan, additional, Axcrona, Karol, additional, Mikropoulos, Christos, additional, Mitra, Anita V, additional, Moynihan, Clare, additional, Ni Raghallaigh, Holly, additional, Rennert, Gad, additional, Collier, Rebecca, additional, Offman, Judith, additional, Kote-Jarai, Zsofia, additional, Eeles, Rosalind A, additional, Adams, Lisa, additional, Adlard, Julian, additional, Alfonso, Rosa, additional, Ali, Saira, additional, Andrew, Angela, additional, Araújo, Luís, additional, Azam, Nazya, additional, Ball, Darran, additional, Barker, Queenstone, additional, Basevitch, Alon, additional, Benton, Barbara, additional, Berlin, Cheryl, additional, Bermingham, Nicola, additional, Biller, Leah, additional, Bloss, Angela, additional, Bradford, Matilda, additional, Bradshaw, Nicola, additional, Branson, Amy, additional, Brendler, Charles, additional, Brennan, Maria, additional, Bulman, Barbara, additional, Burgess, Lucy, additional, Cahill, Declan, additional, Callard, Alice, additional, Calvo Verges, Nuria, additional, Cardoso, Marta, additional, Carter, Vanda, additional, Catanzaro, Mario, additional, Chamberlain, Anthony, additional, Chapman, Cyril, additional, Chong, Michael, additional, Clark, Caroline, additional, Clowes, Virginia, additional, Cogley, Lyn, additional, Cole, Trevor, additional, Compton, Cecilia, additional, Conner, Tom, additional, Cookson, Sandra, additional, Cornford, Philip, additional, Costello, Philandra, additional, Coulier, Laura, additional, Davies, Michaela, additional, Dechet, Christopher, additional, DeSouza, Bianca, additional, Devlin, Gemma, additional, Douglas, Fiona, additional, Douglas, Emma, additional, Dudakia, Darshna, additional, Duncan, Alexis, additional, Ellery, Natalie, additional, Everest, Sarah, additional, Freemantle, Sue, additional, Frydenberg, Mark, additional, Fuller, Debbie, additional, Gabriel, Camila, additional, Gale, Madeline, additional, Garcia, Lynda, additional, Gay, Simona, additional, Genova, Elena, additional, George, Angela, additional, Georgiou, Demetra, additional, Gisbert, Alexandra, additional, Gleeson, Margaret, additional, Glover, Wayne, additional, Gnanapragasam, Vincent, additional, Goff, Sally, additional, Goldgar, David, additional, Gonçalves, Nuno, additional, Goodman, Selina, additional, Gorrie, Jennifer, additional, Gott, Hannah, additional, Grant, Anna, additional, Gray, Catherine, additional, Griffiths, Julie, additional, Gupwell, Karin, additional, Gurasashvili, Jana, additional, Hanslien, Eldbjørg, additional, Haraldsdottir, Sigurdis, additional, Hart, Rachel, additional, Hartigan, Catherine, additional, Hawkes, Lara, additional, Heaton, Tricia, additional, Henderson, Alex, additional, Henrique, Rui, additional, Hilario, Kathrine, additional, Hill, Kathryn, additional, Hulick, Peter, additional, Hunt, Clare, additional, Hutchings, Melanie, additional, Ibitoye, Rita, additional, Inglehearn, Thomas, additional, Ireland, Joanna, additional, Islam, Farah, additional, Ismail, Siti, additional, Jacobs, Chris, additional, James, Denzil, additional, Jenkins, Sharon, additional, Jobson, Irene, additional, Johnstone, Anne, additional, Jones, Oliver, additional, Josefsberg Ben-Yehoshua, Sagi, additional, Kaemba, Beckie, additional, Kaul, Karen, additional, Kemp, Zoe, additional, Kinsella, Netty, additional, Klehm, Margaret, additional, Kockelbergh, Roger, additional, Kohut, Kelly, additional, Kosicka-Slawinska, Monika, additional, Kulkarni, Anjana, additional, Kumar, Pardeep, additional, Lam, Jimmy, additional, LeButt, Mandy, additional, Leibovici, Dan, additional, Lim, Ramona, additional, Limb, Lauren, additional, Lomas, Claire, additional, Longmuir, Mark, additional, López, Consol, additional, Magnani, Tiziana, additional, Maia, Sofia, additional, Maiden, Jessica, additional, Male, Alison, additional, Manalo, Merrie, additional, Martin, Phoebe, additional, McBride, Donna, additional, McGuire, Michael, additional, McMahon, Romayne, additional, McNally, Claire, additional, McVeigh, Terri, additional, Melzer, Ehud, additional, Mencias, Mark, additional, Mercer, Catherine, additional, Mitchell, Gillian, additional, Mora, Josefina, additional, Morton, Catherine, additional, Moss, Cathryn, additional, Murphy, Morgan, additional, Murphy, Declan, additional, Mzazi, Shumi, additional, Nadolski, Maria, additional, Newlin, Anna, additional, Nogueira, Pedro, additional, O'Keefe, Rachael, additional, O'Toole, Karen, additional, O'Connell, Shona, additional, Ogden, Chris, additional, Okoth, Linda, additional, Oliveira, Jorge, additional, Paez, Edgar, additional, Palou, Joan, additional, Park, Linda, additional, Patel, Nafisa, additional, Paulo Souto, João, additional, Pearce, Allison, additional, Peixoto, Ana, additional, Perez, Kimberley, additional, Petelin, Lara, additional, Pichert, Gabriella, additional, Poile, Charlotte, additional, Potter, Alison, additional, Preitner, Nadia, additional, Purnell, Helen, additional, Quinn, Ellen, additional, Radice, Paolo, additional, Rankin, Brigette, additional, Rees, Katie, additional, Renton, Caroline, additional, Richardson, Kate, additional, Risby, Peter, additional, Rogers, Jason, additional, Ruderman, Maggie, additional, Ruiz, April, additional, Sajoo, Anaar, additional, Salvatore, Natale, additional, Sands, Victoria, additional, Sanguedolce, Francesco, additional, Sattar, Ayisha, additional, Saunders, Kathryn, additional, Schofield, Lyn, additional, Scott, Rodney, additional, Searle, Anne, additional, Sehra, Ravinder, additional, Selkirk, Christina, additional, Shackleton, Kylie, additional, Shanley, Sue, additional, Shaw, Adam, additional, Shevrin, Daniel, additional, Shipman, Hannah, additional, Sidat, Zahirah, additional, Siguake, Kas, additional, Simon, Kate, additional, Smyth, Courtney, additional, Snadden, Lesley, additional, Solanky, Nita, additional, Solomons, Joyce, additional, Sorrentino, Margherita, additional, Stayner, Barbara, additional, Stephenson, Robert, additional, Stoffel, Elena, additional, Thomas, Maggie, additional, Thompson, Alan, additional, Tidey, Lizzie, additional, Tischkowitz, Marc, additional, Torokwa, Audrey, additional, Townshend, Sharron, additional, Treherne, Katy, additional, Tricker, Karen, additional, Trinh, Quoc-Dien, additional, Tripathi, Vishakha, additional, Turnbull, Clare, additional, Valdagni, Riccardo, additional, Van As, Nicholas, additional, Venne, Vickie, additional, Verdon, Lizzie, additional, Vitellaro, Marco, additional, Vogel, Kristen, additional, Walker, Lisa, additional, Watford, Amy, additional, Watt, Cathy, additional, Weintroub, Ilana, additional, Weiss, Shelly, additional, Weissman, Scott, additional, Weston, Michelle, additional, Wiggins, Jennifer, additional, Wise, Gillian, additional, Woodhouse, Christopher, additional, Yesildag, Pembe, additional, Youngs, Alice, additional, Yurgelun, Matthew, additional, and Zollo, Fabiana, additional

Published
2021
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50. PD34-12 MRI FINDINGS IN DE NOVO SYNCHRONOUS METASTATIC PROSTATE CANCER AND IMPLICATIONS FOR CYTOREDUCTIVE SURGERY

Author

Connor, Martin John, primary, Edison, Marie, additional, Bass, Edward J., additional, Eldred-Evans, David, additional, Bertoncelli, Mariana Tanaka, additional, Hrouda, David, additional, Khoubehi, Bijan, additional, Hellawell, Giles, additional, Rai, Bhavan, additional, Dudderidge, Tim, additional, Tam, Henry, additional, Winkler, Mathias, additional, and Ahmed, Hashim U., additional

Published
2021
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