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102. The relevance and implications of signet-ring cell adenocarcinoma of the oesophagus

Author

Bleaney, Christopher William, Barrow, Mickhaiel, Hayes, Stephen, and Ang, Yeng

Abstract

AimTo review the current understanding of signet-ring type oesophageal adenocarcinoma including evidence for prognosis.MethodsWe conducted a literature search of nine healthcare literature databases for articles detailing the biology and clinical outcomes of signet-ring cell adenocarcinoma of the oesophagus. The impact of signet-ring cell morphology was analysed and detailed in written text and tabular format. Current understanding of the biology of signet-ring cell adenocarcinoma of the oesophagus was summarised.ResultsSignet-ring cell carcinoma was represented in 7.61% of the 18 989 cases of oesophageal carcinoma reviewed in multiple studies. The presence of signet-ring cells conferred a worse prognosis and these tumours responded differently to conventional treatments as compared with typical adenocarcinoma. Little is known about the biological features of signet-ring cell adenocarcinoma of the oesophagus. Work in gastric lesions has identified potential targets for future treatments such as CDH1and RHOAgenes. Categorisation of signet-ring cell carcinomas by the proportion of signet-ring cells within tumours differs among clinicians despite WHO criteria for classification. The current UK guidelines for histopathological reporting of oesophageal tumours do not emphasise the importance of identifying signet-ring cells.ConclusionThe presence of signet-ring cells in oesophageal adenocarcinomas leads to poorer clinical outcomes. Current understanding of signet-ring cell biology in oesophageal cancer is limited.

Published
2018
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103. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.

Author

Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, Jankowski, Janusz A Z, Su, Zhan, Gay, Laura J, Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C, Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Céline, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T, Pirinen, Matti, Peppelenbosch, Maikel P, van der Laan, Luc J W, Kuipers, Ernst J, Drenth, Joost P H, Peters, Wilbert H, Reynolds, John V, Kelleher, Dermot P, McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D, van Baal, Jantine W P M, Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H, Bird, Nigel C, Dallal, Helen, Shaheen, Nicholas J, Murray, Liam J, Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J, Zhang, Rui, Winter, Helen, Corley, Douglas A, Panter, Simon, Risch, Harvey A, Reid, Brian J, Sargeant, Ian, Gammon, Marilie D, Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G, Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M, Gellatly, Nichola L, Glancy, Deborah, Cooper, Sheldon C, Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F, Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L, Peltonen, Leena, Spencer, Chris C A, Tomlinson, Ian, Donnelly, Peter, and Jankowski, Janusz A Z

Abstract

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

Published
2012
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104. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus

Author

Fitzgerald, Rebecca C, primary, di Pietro, Massimiliano, additional, Ragunath, Krish, additional, Ang, Yeng, additional, Kang, Jin-Yong, additional, Watson, Peter, additional, Trudgill, Nigel, additional, Patel, Praful, additional, Kaye, Philip V, additional, Sanders, Scott, additional, O'Donovan, Maria, additional, Bird-Lieberman, Elizabeth, additional, Bhandari, Pradeep, additional, Jankowski, Janusz A, additional, Attwood, Stephen, additional, Parsons, Simon L, additional, Loft, Duncan, additional, Lagergren, Jesper, additional, Moayyedi, Paul, additional, Lyratzopoulos, Georgios, additional, and de Caestecker, John, additional

Published
2013
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105. Radiofrequency Ablation and Endoscopic Mucosal Resection for Dysplastic Barrett's Esophagus and Early Esophageal Adenocarcinoma: Outcomes of the UK National Halo RFA Registry

Author

Haidry, Rehan J., primary, Dunn, Jason M., additional, Butt, Mohammed A., additional, Burnell, Matthew G., additional, Gupta, Abhinav, additional, Green, Sarah, additional, Miah, Haroon, additional, Smart, Howard L., additional, Bhandari, Pradeep, additional, Smith, Lesley Ann, additional, Willert, Robert, additional, Fullarton, Grant, additional, Morris, John, additional, Di Pietro, Massimo, additional, Gordon, Charles, additional, Penman, Ian, additional, Barr, Hugh, additional, Patel, Praful, additional, Boger, Philip, additional, Kapoor, Neel, additional, Mahon, Brinder, additional, Hoare, Jonathon, additional, Narayanasamy, Ravi, additional, O'Toole, Dermot, additional, Cheong, Edward, additional, Direkze, Natalie C., additional, Ang, Yeng, additional, Novelli, Marco, additional, Banks, Matthew R., additional, and Lovat, Laurence Bruce, additional

Published
2013
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106. 283 Patients Undergoing Radiofrequency Ablation (RFA) for Barrett's Related Neoplasia Have Improved Outcomes With Decreasing Length's of Baseline Barrett's Eosophagus (BE) and Increasing Number of RFA Sessions

Author

Haidry, Rehan J., primary, Butt, Mohammed a., additional, Gupta, Abhinav, additional, Louis-Auguste, John R., additional, Dunn, Jason M., additional, Smart, Howard, additional, Bhandari, Pradeep, additional, Smith, Lesley Ann, additional, Willert, Robert P., additional, Fullarton, Grant, additional, Di Pietro, Massimiliano, additional, Gordon, Charles, additional, Penman, Ian D., additional, Barr, Hugh, additional, Patel, Praful, additional, Boger, Philip C., additional, Kapoor, Neil, additional, Mahon, Brinder S., additional, Hoare, Jonathan M., additional, Burnell, Matthew, additional, Narayanasamy, Ravi, additional, O'Toole, Dermot, additional, Cheong, Edward, additional, Direkze, Natalie, additional, Ang, Yeng S., additional, Novelli, Marco, additional, Banks, Matthew R., additional, and Lovat, Laurence, additional

Published
2013
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115. The pitfalls of bedside glucometers

Author

Ang Yeng and Richard Keld

Subjects
medicine.medical_specialty, Letter, business.industry, Insulin, medicine.medical_treatment, Continuous ambulatory peritoneal dialysis, General Medicine, Jaundice, Icodextrin, Glucose dehydrogenase, Naloxone, Blood Glucose Self-Monitoring, medicine, Vomiting, medicine.symptom, Intensive care medicine, business, medicine.drug
Abstract

We felt it was important to highlight a problem that we encountered with a bedside glucometer and a patient with end stage renal failure on continuous ambulatory peritoneal dialysis. Vast discrepancies between true venous glucose levels and those estimated by certain glucometers in this situation can be problematic and dangerous. Not all glucometers are the same: they differ in their ability to estimate glucose levels. The Advantage (Roche) and Accutrend Sensor (Boehringer MannHeim) glucometers both use the glucose dehydrogenase enzyme reaction to estimate glucose levels. Certain dialysates, including Extraneal (Icodextrin), contain significant amounts of long-chain non-glucose-reducing substances. Such substances are metabolized by glucose dehydrogenase and lead to falsely elevated glucose readings. Precision Q.I.D (Medisense) and Glucocard (Merarini Diagnostics) glucometers analyse glucose levels using a different enzyme, glucose oxidase. Long-chain non-glucose-reducing substances do not interfere with glucose calculations based on this enzyme. We encountered a young patient on continuous ambulatory peritoneal dialysis in our hospital who was using a Roche glucometer at home. Compliance with treatment seemed poor. The patient had been admitted with severe hypertension and hyperglycaemia. His Extraneal dialysate solutions were adjusted appropriately and a insulin sliding scale was commenced. At this time he had a hypoglycaemic coma that was not diagnosed until after the venous glucose had returned from the laboratory. During this delay he had failed to respond to naloxone and also had a brain CT, which was normal. The Consultant Physician, Nephrology Team and myself were all perplexed by his sudden deterioration. The glucometer read 11 mmol/L. The nursing staff reported that the glucometer had been calibrated by our Biochemistry department and it was the same type used by the patient at home, and that they had also repeated the glucometer reading. Discrepancies have been reported a couple of times in the medical literature, however it seems that a knowledge of this problem is not widespread. This near-miss led to a policy change in our hospital, and the episode emphases the importance of not taking a glucometer reading on face value. Dehydration, vomiting, diarrhoea, diuretics, peripheral vascular disease, hyperuricaemia, significant paracetamol overdose and severe jaundice can also lead to unreliable results.

Published
2008
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116. The TNF region in celiac disease

Author

Daly, Jacqueline, primary, McManus, Ross, additional, Hagan, Richard, additional, Ryan, Anthony, additional, Ryan, Barbara, additional, Ang, Yeng, additional, Farrell, Richard, additional, Weir, Donald, additional, and Kelleher, Dermot, additional

Published
2003
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121. Sex differences in oncogenic mutational processes

Author

Prokopec, Stephenie D., Sun, Ren X., Yousif, Fouad, Schmitz, Nathaniel, Al-Shahrour, Fatima, Atwal, Gurnit, 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., Jiao, Wei, Kaiser, Vera B., Karlić, Rosa, 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., Polak, Paz, Rheinbay, Esther, Rubin, Mark A., Semple, Colin A., Sgroi, Dennis C., Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D., Stobbe, Miranda D., Thai, Kevin, Wright, Derek W., Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, 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 R., 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 D. L., 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 J. C., 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 M. G., 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 L. L., George, Joshy, Gerhard, Daniela S., Gerhauser, Clarissa, Gershenwald, Jeffrey E., Gerstein, Mark, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., 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, S. M. Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose M. G., 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 T. W., Jones, Nic, Jones, Steven J. M., 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, 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 N. 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P., Neal, David E., Nettekoven, Gerd, Newell, Felicity, Newhouse, Steven J., Newton, Yulia, Ng, Alvin Wei Tian, Ng, Anthony, Nicholson, Jonathan, Nicol, David, Nie, Yongzhan, Nielsen, Morten Muhlig, Noble, Michael S., Nones, Katia, Northcott, Paul A., Notta, Faiyaz, O’Connor, Brian D., O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J. Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A., Ojesina, Akinyemi I., Ojima, Hidenori, Okusaka, Takuji, Ong, Chovon Kiat, Ossowski, Stephan, Ott, German, Ouellette, B. F. Francis, 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, Park, Peter J., Parker, Joel S., Parsons, Simon L., Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pearson, John V., Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A., Perou, Charles M., 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, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R., Prinz, Manuel, Pritchard, Antonia L., Provenzano, Elena, Puente, Xose S., Puig, Sonia, Puiggròs, Montserrat, 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., Riazalhosseini, Yasser, Richardson, Andrea L., Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Rippe, Karsten, Roach, Jeffrey, Roberts, Lewis R., Roberts, Nicola D., Roberts, Steven A., Robertson, A. Gordon, Robertson, Alan J., Rodriguez, Javier Bartolomé, Rodriguez-Martin, Bernardo, Rodríguez-González, F. Germán, Roehrl, Michael H. A., 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, 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 P. M., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E., Schilhabel, Markus B., Schlesner, Matthias, Schlomm, Thorsten, Schmidt, Heather K., Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schumacher, Steven E., Schwarz, Roland F., Scolyer, Richard A., Scott, David, Scully, Ralph, Seethala, Raja, Segre, Ayellet V., Selander, Iris, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Shackleton, Mark, 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, 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, Sidiropoulos, Nikos, Sieuwerts, Anieta M., Sieverling, Lina, 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-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, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stratton, Michael R., Stretch, Jonathan R., Struck, Adam J., Stuart, Joshua M., Stunnenberg, Henk G., Su, Hong, Su, Xiaoping, 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, Thayer, Sarah P., Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M., Thompson, John F., 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., Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz H. P., Tsao, Ming, Tsunoda, Tatsuhiko, Tubio, Jose M. C., 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 P. 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Vijay, Viksna, Juris, Vilain, Ricardo E., Villasante, Izar, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M., Waddell, Nicola, Wadelius, Claes, Wadi, Lina, Wagener, Rabea, Wala, Jeremiah A., 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., Weischenfeldt, Joachim, 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, Mark H., 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, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D., Yoon, Christopher J., Yoon, Sung-Soo, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Yuan, Yuen, Denis, Yung, Christina K., Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C., Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, 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 H. M., Van De Vijver, Marc J., Veer, L. Van’t, and Von Mering, Christian

Subjects
692/4028/67/69, ComputingMilieux_THECOMPUTINGPROFESSION, 45, 631/67/68, 692/4028/67/395, 38/23, 631/114/2785, article, ComputingMilieux_LEGALASPECTSOFCOMPUTING, 119, 10. No inequality, GeneralLiterature_MISCELLANEOUS, 3. Good health
Abstract

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790, Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762, Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196, Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376, Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.

122. Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett’s Esophagus

Author

Al Dulaimi, David, Johnson, Matthew, Trynka, Gosia, Prenen, Hans, Atherfold, Paul, Li, Xinzhong, Vaughan, Tom L., Ye, Weimin, Love, Sharon, Van Der Laan, Luc J.W., Boulter, Lisa, Rathbone, Barrie, Shaheen, Nicholas J., Underwood, Tim, Decaestecker, John, Roylance, Rebecca, Chow, Wu, Reid, Brian J., Van Den Brande, Jan, Watson, Peter, Ang, Yeng, Monk, David, Bisschops, Raf, Farrant, Mark, Farnham, Garry, O'Sullivan, Jacintha, Dhar, Anjan, Bernstein, Leslie, Beales, Ian, Toxopeus, Eelke L., Wijmenga, Cisca, Hapeshi, Julie, Tucker, Art, Sanders, Scott, Nwokolo, Chuka, Moayyedi, Paul, Kadri, Sudarshan, Vermeire, Severine, Bird, Nigel C., Barr, Hugh, Ragunath, Krish, Gammon, Marilie D., Liu, Geoffrey, Briggs, Sarah, Castro Giner, Francesc, Harrison, Rebecca, Romero, Yvonne, Patel, Praful, Kelly, Sean, Krishnadath, Kausilia, Casson, Alan G., Cleynen, Isabelle, Macdonald, David, Beckett, Conrad, McGarrigle, Sarah A., Adams, Claire L., Fitzgerald, Rebecca, Reynolds, John V., Dixon, Andrew, Whiteman, David C., Kuipers, Ernst J., McManus, Ross, Wu, Anna H., Tomlinson, Ian, Wijnhoven, Bas P.L., Zietek, Barbara, Risch, Harvey A., Chegwidden, Laura, Rembacken, Bjorn, Mullins, Paul, Haigh, Chris, Corley, Douglas A., Verhaar, Auke P., Trudgill, Nigel, Ferry, David, Palles, Claire, Murray, Iain, Green, Elaine, Nanji, Manoj, Levine, David M., Maroo, Neera, Spaander, Manon C., Wajed, Shahjehan, Kovac, Michal, Sawyer, Elinor, McMurtry, Hugh, Hardie, Laura J., Gay, Laura, Findlay, John M., Paterson, Stuart, Peppelenbosch, Maikel P., Veitch, Andrew, Grimley, Charles, Macmathuna, Padraic, Onstad, Lynn, Koss, Konrad, Kelleher, Dermot, and Jankowski, Janusz

Subjects
3. Good health
Abstract

Background & AimsBarrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.MethodsWe performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.ResultsWe identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR]= 1.14; 95% CI: 1.09–1.18; P= 1.8× 10−11) and rs2701108 (12q24.21; OR= 0.90; 95% CI: 0.86–0.93; P= 7.5× 10−9). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNPassociated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR= 0.90; 95% CI: 0.87–0.93; P=3.72× 10−9).ConclusionsWe identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

123. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Author

Meyerson, William U., Dursi, Lewis Jonathan, Wang, Liang-Bo, Dong, Guanlan, Liang, Wen-Wei, Weerasinghe, Amila, Li, Yize, Kelso, Sean, Wendl, Michael C., Simpson, Jared T., Akbani, Rehan, Anur, Pavana, Bailey, Matthew H., Buchanan, Alex, Chiotti, Kami, Covington, Kyle, Creason, Allison, Ding, Li, Ellrott, Kyle, Fan, Yu, Foltz, Steven, Getz, Gad, Hale, Walker, Haussler, David, Hess, Julian M., Hutter, Carolyn M., Kandoth, Cyriac, Kasaian, Katayoon, Kasapi, Melpomeni, Larson, Dave, Leshchiner, Ignaty, Letaw, John, Ma, Singer, McLellan, Michael D., Men, Yifei, Mills, Gordon B., Niu, Beifang, Peto, Myron, Radenbaugh, Amie, Reynolds, Sheila M., Saksena, Gordon, Sofia, Heidi, Stewart, Chip, Struck, Adam J., Stuart, Joshua M., Wang, Wenyi, Weinstein, John N., Wheeler, David A., Wong, Christopher K., Xi, Liu, Ye, Kai, Bieg, Matthias, Boutros, Paul C., Buchhalter, Ivo, Butler, Adam P., Chen, Ken, Chong, Zechen, Drechsel, Oliver, Jonathan Dursi, Lewis, Eils, Roland, Espiritu, Shadrielle M. G., Fulton, Robert S., Gao, Shengjie, Gelpi, Josep L. L., Gerstein, Mark B., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael C., Hinton, Jonathan, Hu, Taobo, Huang, Vincent, Huang, Yi, Hutter, Barbara, Jones, David R., Jung, Jongsun, Jäger, Natalie, Kim, Hyung-Lae, Kleinheinz, Kortine, Kumar, Sushant, Kumar, Yogesh, Lalansingh, Christopher M., Letunic, Ivica, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Mashl, R. Jay, Menzies, Andrew, Milovanovic, Ana, Nielsen, Morten Muhlig, Ossowski, Stephan, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Perry, Marc D., Puiggròs, Montserrat, Raine, Keiran M., Rheinbay, Esther, Royo, Romina, Sahinalp, S. Cenk, Sarrafi, Iman, Schlesner, Matthias, Stebbings, Lucy, Stobbe, Miranda D., Teague, Jon W., Tiao, Grace, Torrents, David, Wala, Jeremiah A., Wang, Jiayin, Waszak, Sebastian M., Weischenfeldt, Joachim, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yakneen, Sergei, Yamaguchi, Takafumi N., Yellapantula, Venkata D., Yung, Christina K., Zhang, Junjun, Aaltonen, Lauri A., Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J., Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, 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, 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. 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C., Bruzos, Alicia L., Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H., Busanovich, John, Bustamante, Carlos D., 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, Campbell, Peter J., 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., Chang, David K., Chanock, Stephen J., Chantrill, Lorraine A., Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, 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, 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., Cooke, Susanna L., Cooper, Colin S., Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G., Cordner, Stephen M., Cortés-Ciriano, Isidro, 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, Deshpande, Vikram, Deshwar, Amit G., Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C., Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Shuai, Dinh, Huy Q., Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T., Drapkin, Ronny, Drews, Ruben M., Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J., Dunn, Michael, 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, El-Naggar, Adel, Eldridge, Matthew, Erkek, Serap, Escaramis, Georgia, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E., Faltas, Bishoy M., Fan, Daiming, Faquin, William C., 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., Furuta, Mayuko, Futreal, P. Andrew, Füllgrabe, Anja, Gabriel, Stacey B., Gallinger, Steven, Gambacorti-Passerini, Carlo, Gao, Jianjiong, Garraway, Levi, Garred, Øystein, Garrison, Erik, Garsed, Dale W., Gehlenborg, Nils, George, Joshy, Gerhard, Daniela S., Gerhauser, Clarissa, Gershenwald, Jeffrey E., Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gill, Anthony J., Gill, Pelvender, Giri, Dilip D., Glodzik, Dominik, Gnanapragasam, Vincent J., Goebler, Maria Elisabeth, Goldman, Mary J., Gomez, Carmen, 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, Grimmond, Sean M., Grossman, Robert L., Grundhoff, Adam, Gundem, Gunes, Guo, Qianyun, Gupta, Manaswi, Gupta, Shailja, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haan, David, Haas, Siegfried, Haase, Kerstin, Haber, James E., Habermann, Nina, Haider, Syed, 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, 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., Heins, Zachary, Heisler, Lawrence E., Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J., Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hilmarsdottir, Holmfridur, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hoadley, Katherine A., 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, Hua, Xing, Huang, Kuan-Lin, Huang, Mei, Huang, Mi Ni, Huber, Wolfgang, Hudson, Thomas J., Hummel, Michael, Hung, Jillian A., Huntsman, David, Hupp, Ted R., Huse, Jason, Huska, Matthew R., Hübschmann, Daniel, Iacobuzio-Donahue, Christine A., Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B., Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, S. M. Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose M. G., 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, Jiao, Wei, 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 T. W., Jones, Nic, Jones, Steven J. M., Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Juul, Malene, Juul, Randi Istrup, Juul, Sissel, Kabbe, Rolf, Kahles, Andre, Kahraman, Abdullah, Kaiser, Vera B., Kakavand, Hojabr, Kalimuthu, Sangeetha, Von Kalle, Christof, Kang, Koo Jeong, Karaszi, Katalin, Karlan, Beth, Karlić, Rosa, Karsch, Dennis, Kassahn, Karin S., Katai, Hitoshi, Kato, Mamoru, 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 N. A., Khoo, David, Khoo, Vincent, Khuntikeo, Narong, Khurana, Ekta, Kilpinen, Helena, Kim, Hark Kyun, Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jaegil, Kim, Jihoon, Kim, Jong K., Kim, Youngwook, King, Tari A., Klapper, Wolfram, 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, Kundra, Ritika, Kübler, Kirsten, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H., Laird, Peter W., Lakhani, Sunil R., 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 M. S., Lawerenz, Chris, Lawlor, Rita T., Lawrence, Michael S., Lazar, Alexander J., 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., Letourneau, Louis, 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, Li, Yilong, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Lin, Ziao, Linehan, W. M., Lingjærde, Ole Christian, Liu, Dongbing, Liu, Eric Minwei, Liu, Fei-Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, 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., Lynch, Andy G., Lype, Lisa, López, Cristina, López-Otín, Carlos, 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 W. M., Martin, Sancha, Martin-Subero, Jose I., Martincorena, Iñigo, Martinez-Fundichely, Alexander, Massie, Charlie E., Matthew, Thomas J., Matthews, Lucy, Mayer, Erik, Mayes, Simon, Mayo, Michael, Mbabaali, Faridah, McCune, Karen, McDermott, Ultan, McGillivray, Patrick D., McPherson, John D., McPherson, John R., McPherson, Treasa A., Meier, Samuel R., Meng, Alice, Meng, Shaowu, Merrett, Neil D., Merson, Sue, Meyerson, Matthew, Mieczkowski, Piotr A., Mihaiescu, George L., Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Mikkelsen, Tom, Milella, Michele, Mileshkin, Linda, Miller, Christopher A., Miller, David K., Miller, Jessica K., 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, Morris, Quaid D., Morrison, Carl, Mose, Lisle E., Moser, Catherine D., Muiños, Ferran, Mularoni, Loris, Mungall, Andrew J., Mungall, Karen, Musgrove, Elizabeth A., Mustonen, Ville, Mutch, David, Muyas, Francesc, Muzny, Donna M., Muñoz, Alfonso, Myers, Jerome, Myklebost, Ola, Möller, Peter, Nagae, Genta, Nagrial, Adnan M., Nahal-Bose, Hardeep K., Nakagama, Hitoshi, Nakagawa, Hidewaki, Nakamura, Hiromi, Nakamura, Toru, Nakano, Kaoru, Nandi, Tannistha, Nangalia, Jyoti, Nastic, Mia, Navarro, Arcadi, Navarro, Fabio C. P., Neal, David E., Nettekoven, Gerd, Newell, Felicity, Newhouse, Steven J., Newton, Yulia, Ng, Alvin Wei Tian, Ng, Anthony, Nicholson, Jonathan, Nicol, David, Nie, Yongzhan, Nielsen, G. Petur, Nik-Zainal, Serena, Noble, Michael S., Nones, Katia, Northcott, Paul A., Notta, Faiyaz, O’Connor, Brian D., O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J. Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A., Ojesina, Akinyemi I., Ojima, Hidenori, Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ott, German, Ouellette, B. F. Francis, P’ng, Christine, Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Park, Peter J., Parker, Joel S., Parsons, Simon L., Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pearson, John V., Pedamallu, Chandra Sekhar, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A., Perou, Charles M., Petersen, Gloria M., 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, 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., Riazalhosseini, Yasser, Richardson, Andrea L., Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Rippe, Karsten, Roach, Jeffrey, Roberts, Lewis R., Roberts, Nicola D., Roberts, Steven A., Robertson, A. Gordon, Robertson, Alan J., Rodriguez, Javier Bartolomé, Rodriguez-Martin, Bernardo, Rodríguez-González, F. Germán, Roehrl, Michael H. A., Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C., Rosenwald, Andreas, Rowe, Edward W., 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, Saini, Natalie, Saito-Adachi, Mihoko, 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, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn P. M., 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, Schumacher, Steven E., Schwarz, Roland F., Scolyer, Richard A., Scott, David, Scully, Ralph, Seethala, Raja, Segre, Ayellet V., Selander, Iris, Semple, Colin A., Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Sgroi, Dennis C., Shackleton, Mark, 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, Sidiropoulos, Nikos, Siebert, Reiner, Sieuwerts, Anieta M., Sieverling, Lina, Signoretti, Sabina, Sikora, Katarzyna O., Simbolo, Michele, Simon, Ronald, Simons, Janae V., 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., Stefánsson, Ólafur Andri, Stegle, Oliver, Stein, Lincoln D., Stenhouse, Alasdair, Stilgenbauer, Stephan, Stratton, Michael R., Stretch, Jonathan R., 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, 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 F., Thompson, R. Houston, Thorne, Heather, Thorne, Leigh B., Thorogood, Adrian, 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 H. P., Tsao, Ming, Tsunoda, Tatsuhiko, Tubio, Jose M. C., 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 P. C., Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, Raghavan, K. 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M., Van De Vijver, Marc J., Van’t Veer, L., and Von Mering, Christian

Subjects
692/4028/67/69, 706/648/697/129/2043, 631/114/2399, article, 45/23, 139, 631/1647/2217/748, 3. Good health
Abstract

Funder: NCI U24CA211006, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.

124. Sex differences in oncogenic mutational processes

Author

Prokopec, Stephenie D., Sun, Ren X., Yousif, Fouad, Schmitz, Nathaniel, Al-Shahrour, Fatima, Atwal, Gurnit, 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., Jiao, Wei, Kaiser, Vera B., Karlić, Rosa, 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., Polak, Paz, Rheinbay, Esther, Rubin, Mark A., Semple, Colin A., Sgroi, Dennis C., Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D., Stobbe, Miranda D., Thai, Kevin, Wright, Derek W., Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, 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 R., 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. 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G., 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 L. 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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, S. M. Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose M. G., 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 T. W., Jones, Nic, Jones, Steven J. M., 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, 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 N. A., 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 M. S., Lawerenz, Chris, Lawlor, Rita T., Lawrence, Michael S., 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, W. M., Lingjærde, Ole Christian, Liu, Dongbing, Liu, Eric Minwei, Liu, 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, Ma, Eric Z., 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 W. 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P., Neal, David E., Nettekoven, Gerd, Newell, Felicity, Newhouse, Steven J., Newton, Yulia, Ng, Alvin Wei Tian, Ng, Anthony, Nicholson, Jonathan, Nicol, David, Nie, Yongzhan, Nielsen, Morten Muhlig, Noble, Michael S., Nones, Katia, Northcott, Paul A., Notta, Faiyaz, O’Connor, Brian D., O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J. Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A., Ojesina, Akinyemi I., Ojima, Hidenori, Okusaka, Takuji, Ong, Chovon Kiat, Ossowski, Stephan, Ott, German, Ouellette, B. F. Francis, 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, Park, Peter J., Parker, Joel S., Parsons, Simon L., Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pearson, John V., Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A., Perou, Charles M., 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, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R., Prinz, Manuel, Pritchard, Antonia L., Provenzano, Elena, Puente, Xose S., Puig, Sonia, Puiggròs, Montserrat, 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., Riazalhosseini, Yasser, Richardson, Andrea L., Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Rippe, Karsten, Roach, Jeffrey, Roberts, Lewis R., Roberts, Nicola D., Roberts, Steven A., Robertson, A. Gordon, Robertson, Alan J., Rodriguez, Javier Bartolomé, Rodriguez-Martin, Bernardo, Rodríguez-González, F. Germán, Roehrl, Michael H. A., 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, 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 P. M., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E., Schilhabel, Markus B., Schlesner, Matthias, Schlomm, Thorsten, Schmidt, Heather K., Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schumacher, Steven E., Schwarz, Roland F., Scolyer, Richard A., Scott, David, Scully, Ralph, Seethala, Raja, Segre, Ayellet V., Selander, Iris, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Shackleton, Mark, 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, 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, Sidiropoulos, Nikos, Sieuwerts, Anieta M., Sieverling, Lina, 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-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, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stratton, Michael R., Stretch, Jonathan R., Struck, Adam J., Stuart, Joshua M., Stunnenberg, Henk G., Su, Hong, Su, Xiaoping, 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, Thayer, Sarah P., Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M., Thompson, John F., 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., Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz H. P., Tsao, Ming, Tsunoda, Tatsuhiko, Tubio, Jose M. C., 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 P. C., Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, Raghavan, K. Vijay, Viksna, Juris, Vilain, Ricardo E., Villasante, Izar, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M., Waddell, Nicola, Wadelius, Claes, Wadi, Lina, Wagener, Rabea, Wala, Jeremiah A., 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., Weischenfeldt, Joachim, 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, Mark H., 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, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D., Yoon, Christopher J., Yoon, Sung-Soo, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Yuan, Yuen, Denis, Yung, Christina K., Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C., Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, 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 H. M., Van De Vijver, Marc J., Veer, L. Van’t, and Von Mering, Christian

Subjects
692/4028/67/69, ComputingMilieux_THECOMPUTINGPROFESSION, 45, 631/67/68, 692/4028/67/395, 38/23, 631/114/2785, article, ComputingMilieux_LEGALASPECTSOFCOMPUTING, 119, 10. No inequality, GeneralLiterature_MISCELLANEOUS, 3. Good health
Abstract

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790, Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762, Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196, Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376, Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.

125. Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

Author

Palles, Claire, Chegwidden, Laura, Li, Xinzhong, Findlay, John M, Farnham, Garry, Castro Giner, Francesc, Peppelenbosch, Maikel P, Kovac, Michal, Adams, Claire L, Prenen, Hans, Briggs, Sarah, Harrison, Rebecca, Sanders, Scott, MacDonald, David, Haigh, Chris, Tucker, Art, Love, Sharon, Nanji, Manoj, DeCaestecker, John, Ferry, David, Rathbone, Barrie, Hapeshi, Julie, Barr, Hugh, Moayyedi, Paul, Watson, Peter, Zietek, Barbara, Maroo, Neera, Gay, Laura, Underwood, Tim, Boulter, Lisa, McMurtry, Hugh, Monk, David, Patel, Praful, Ragunath, Krish, Al Dulaimi, David, Murray, Iain, Koss, Konrad, Veitch, Andrew, Trudgill, Nigel, Nwokolo, Chuka, Rembacken, Bjorn, Atherfold, Paul, Green, Elaine, Ang, Yeng, Kuipers, Ernst J, Chow, Wu, Paterson, Stuart, Kadri, Sudarshan, Beales, Ian, Grimley, Charles, Mullins, Paul, Beckett, Conrad, Farrant, Mark, Dixon, Andrew, Kelly, Sean, Johnson, Matthew, Wajed, Shahjehan, Dhar, Anjan, Sawyer, Elinor, Roylance, Rebecca, Onstad, Lynn, Gammon, Marilie D, Corley, Douglas A, Shaheen, Nicholas J, Bird, Nigel C, Hardie, Laura J, Reid, Brian J, Ye, Weimin, Liu, Geoffrey, Romero, Yvonne, Bernstein, Leslie, Wu, Anna H, Casson, Alan G, Fitzgerald, Rebecca, Whiteman, David C, Risch, Harvey A, Levine, David M, Vaughan, Tom L, Verhaar, Auke P, Van Den Brande, Jan, Toxopeus, Eelke L, Spaander, Manon C, Wijnhoven, Bas PL, Van Der Laan, Luc JW, Krishnadath, Kausilia, Wijmenga, Cisca, Trynka, Gosia, McManus, Ross, Reynolds, John V, O'Sullivan, Jacintha, MacMathuna, Padraic, McGarrigle, Sarah A, Kelleher, Dermot, Vermeire, Severine, Cleynen, Isabelle, Bisschops, Raf, Tomlinson, Ian, and Jankowski, Janusz

Subjects
Risk, Esophageal Neoplasms, Polymorphism, Single Nucleotide, 3. Good health, Growth Differentiation Factors, Intestinal Metaplasia, Barrett Esophagus, Susceptibility, Bone Morphogenetic Proteins, Humans, Genetic Predisposition to Disease, EAC, T-Box Domain Proteins, Cancer, Genome-Wide Association Study
Abstract

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

126. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Author

Meyerson, William U., Dursi, Lewis Jonathan, Wang, Liang-Bo, Dong, Guanlan, Liang, Wen-Wei, Weerasinghe, Amila, Kelso, Sean, Wendl, Michael C., Simpson, Jared T., Akbani, Rehan, Anur, Pavana, Bailey, Matthew H., Buchanan, Alex, Chiotti, Kami, Covington, Kyle, Creason, Allison, Ding, Li, Ellrott, Kyle, Fan, Yu, Foltz, Steven, Getz, Gad, Hale, Walker, Haussler, David, Hess, Julian M., Hutter, Carolyn M., Kandoth, Cyriac, Kasaian, Katayoon, Kasapi, Melpomeni, Larson, Dave, Leshchiner, Ignaty, Letaw, John, Ma, Singer, McLellan, Michael D., Men, Yifei, Mills, Gordon B., Niu, Beifang, Peto, Myron, Radenbaugh, Amie, Reynolds, Sheila M., Saksena, Gordon, Sofia, Heidi, Stewart, Chip, Struck, Adam J., Stuart, Joshua M., Wang, Wenyi, Weinstein, John N., Wheeler, David A., Wong, Christopher K., Xi, Liu, Ye, Kai, Bieg, Matthias, Boutros, Paul C., Buchhalter, Ivo, Butler, Adam P., Chen, Ken, Chong, Zechen, Drechsel, Oliver, Jonathan Dursi, Lewis, Eils, Roland, Espiritu, Shadrielle M. G., Fulton, Robert S., Gao, Shengjie, Gelpi, Josep L. L., Gerstein, Mark B., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael C., Hinton, Jonathan, Hu, Taobo, Huang, Vincent, Huang, Yi, Hutter, Barbara, Jones, David R., Jung, Jongsun, Jäger, Natalie, Kim, Hyung-Lae, Kleinheinz, Kortine, Kumar, Sushant, Kumar, Yogesh, Lalansingh, Christopher M., Letunic, Ivica, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Mashl, R. Jay, Menzies, Andrew, Milovanovic, Ana, Nielsen, Morten Muhlig, Ossowski, Stephan, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Perry, Marc D., Puiggròs, Montserrat, Raine, Keiran M., Rheinbay, Esther, Royo, Romina, Sahinalp, S. Cenk, Sarrafi, Iman, Schlesner, Matthias, Stebbings, Lucy, Stobbe, Miranda D., Teague, Jon W., Tiao, Grace, Torrents, David, Wala, Jeremiah A., Wang, Jiayin, Waszak, Sebastian M., Weischenfeldt, Joachim, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yakneen, Sergei, Yamaguchi, Takafumi N., Yellapantula, Venkata D., Yung, Christina K., Zhang, Junjun, Aaltonen, Lauri A., Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J., Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, 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, 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 R., Awadalla, Philip, Aymerich, Marta, Bader, Gary D., Baez-Ortega, Adrian, Bailey, Peter J., 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, 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., Biankin, Andrew V., 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 D. L., 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 J. 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M., Van De Vijver, Marc J., Van’t Veer, L., and Von Mering, Christian

Subjects
692/4028/67/69, 706/648/697/129/2043, 631/114/2399, article, 45/23, 139, 631/1647/2217/748, 3. Good health
Abstract

Funder: NCI U24CA211006, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.

127. Pan-cancer analysis of whole genomes

Author

Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O’Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon I., Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet V., Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Heredia-Genestar, José María, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-Lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Taylor-Weiner, Amaro, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortés-Ciriano, Isidro, Urban, Lara, Park, Peter, Zhu, Bin, Pitkänen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Rätsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnár-Gábor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Piñeiro-Yáñez, Elena, Muñoz, Alfonso, Petryszak, Robert, Füllgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jäger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggròs, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Jüri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, André, Lehmann, Kjong-Van, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioğlu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurélien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi I., Pan-Hammarström, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Göke, Jonathan, Zhang, Zemin, Brooks, Angela N., Fittall, Matthew W, Martincorena, Iñigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshøj, Henrik, Deu-Pons, Jordi, Muiños, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Hübschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kahles, Andre, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, Von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Rémi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Søren, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Rory, Juul, Randi Istrup, Kim, Jaegil, Kim, Jong K., Komorowski, Jan, Lanzós, Andrés, Larsson, Erik, Lee, Donghoon, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martinez-Fundichely, Alexander, McGillivray, Patrick D., Meyerson, William, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes-Salazar, Iker, Reyna, Matthew A., Rubin, Mark A., Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Tsunoda, Tatsuhiko, Umer, Husen M., Uusküla-Reimand, Liis, Verbeke, Lieven P. C., Wadelius, Claes, Wadi, Lina, Warrell, Jonathan, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, Lawrence, Michael S., Raphael, Benjamin J., Bailey, Peter J., Craft, David, Goldman, Mary J., Aburatani, Hiroyuki, Binder, Hans, Dinh, Huy Q., Heath, Simon C., Hoffmann, Steve, Imbusch, Charles David, Kretzmer, Helene, Laird, Peter W., Martin-Subero, Jose I., Nagae, Genta, Shen, Hui, Wang, Qi, Weichenhan, Dieter, Zhou, Wanding, Berman, Benjamin P., Brors, Benedikt, Plass, Christoph, Akdemir, Kadir C., Bowtell, David D. L., Burns, Kathleen H., Busanovich, John, Chan, Kin, Dueso-Barroso, Ana, Edwards, Paul A., Etemadmoghadam, Dariush, Haber, James E., Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Koh, Youngil, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Navarro, Fabio C. P., Pearson, John V., Rippe, Karsten, Scully, Ralph, Villasante, Izar, Waddell, Nicola, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zhang, Cheng-Zhong, Bergstrom, Erik N., Boot, Arnoud, Covington, Kyle, Fujimoto, Akihiro, Huang, Mi Ni, Islam, S. M. Ashiqul, McPherson, John R., Morganella, Sandro, Mustonen, Ville, Ng, Alvin Wei Tian, Prokopec, Stephenie D., Vázquez-García, Ignacio, Wu, Yang, Yousif, Fouad, Yu, Willie, Rozen, Steven G., Rudneva, Vasilisa A., Shringarpure, Suyash S., Turner, Daniel J., Xia, Tian, Atwal, Gurnit, Chang, David K., Cooke, Susanna L., Faltas, Bishoy M., Haider, Syed, Kaiser, Vera B., Karlić, Rosa, Kato, Mamoru, Kübler, Kirsten, Margolin, Adam, Martin, Sancha, Nik-Zainal, Serena, P’ng, Christine, Semple, Colin A., Smith, Jaclyn, Sun, Ren X., Thai, Kevin, Wright, Derek W., Yuan, Ke, Biankin, Andrew V., Garraway, Levi, Grimmond, Sean M., Adams, David J., Anur, Pavana, Cao, Shaolong, Christie, Elizabeth L., Cmero, Marek, Cun, Yupeng, Dawson, Kevin J., Dentro, Stefan C., Deshwar, Amit G., Donmez, Nilgun, Drews, Ruben M., Gerstung, Moritz, Ha, Gavin, Haase, Kerstin, Jerman, Lara, Ji, Yuan, Jolly, Clemency, Lee, Juhee, Lee-Six, Henry, Malikic, Salem, Mitchell, Thomas J., Morris, Quaid D., Oesper, Layla, Peifer, Martin, Peto, Myron, Rosebrock, Daniel, Rubanova, Yulia, Salcedo, Adriana, Sengupta, Subhajit, Shi, Ruian, Shin, Seung Jun, Spiro, Oliver, Vembu, Shankar, Wintersinger, Jeffrey A., Yang, Tsun-Po, Yu, Kaixian, Zhu, Hongtu, Spellman, Paul T., Weinstein, John N., Chen, Yiwen, Fujita, Masashi, Han, Leng, Hasegawa, Takanori, Komura, Mitsuhiro, Li, Jun, Mizuno, Shinichi, Shimizu, Eigo, Wang, Yumeng, Xu, Yanxun, Yamaguchi, Rui, Yang, Fan, Yang, Yang, Yoon, Christopher J., Yuan, Yuan, Liang, Han, Alawi, Malik, Borozan, Ivan, Brewer, Daniel S., Cooper, Colin S., Desai, Nikita, Grundhoff, Adam, Iskar, Murat, Su, Xiaoping, Zapatka, Marc, Lichter, Peter, Alsop, Kathryn, Bruxner, Timothy J. C., Christ, Angelika N., Cordner, Stephen M., Cowin, Prue A., Drapkin, Ronny, Fereday, Sian, George, Joshy, Hamilton, Anne, Holmes, Oliver, Hung, Jillian A., Kassahn, Karin S., Kazakoff, Stephen H., Kennedy, Catherine J., Leonard, Conrad R., Mileshkin, Linda, Miller, David K., Arnau, Gisela Mir, Mitchell, Chris, Newell, Felicity, Nones, Katia, Patch, Ann-Marie, Quinn, Michael C., Taylor, Darrin F., Thorne, Heather, Traficante, Nadia, Vedururu, Ravikiran, Waddell, Nick M., Waring, Paul M., Wood, Scott, Xu, Qinying, DeFazio, Anna, Anderson, Matthew J., Antonello, Davide, Barbour, Andrew P., Bassi, Claudio, Bersani, Samantha, Cataldo, Ivana, Chantrill, Lorraine A., Chiew, Yoke-Eng, Chou, Angela, Cingarlini, Sara, Cloonan, Nicole, Corbo, Vincenzo, Davi, Maria Vittoria, Duthie, Fraser R., Gill, Anthony J., Graham, Janet S., Harliwong, Ivon, Jamieson, Nigel B., Johns, Amber L., Kench, James G., Landoni, Luca, Lawlor, Rita T., Mafficini, Andrea, Merrett, Neil D., Miotto, Marco, Musgrove, Elizabeth A., Nagrial, Adnan M., Oien, Karin A., Pajic, Marina, Pinese, Mark, Robertson, Alan J., Rooman, Ilse, Rusev, Borislav C., Samra, Jaswinder S., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Sereni, Elisabetta, Sikora, Katarzyna O., Simbolo, Michele, Taschuk, Morgan L., Toon, Christopher W., Vicentini, Caterina, Wu, Jianmin, Zeps, Nikolajs, Behren, Andreas, Burke, Hazel, Cebon, Jonathan, Dagg, Rebecca A., De Paoli-Iseppi, Ricardo, Dutton-Regester, Ken, Field, Matthew A., Fitzgerald, Anna, Hersey, Peter, Jakrot, Valerie, Johansson, Peter A., Kakavand, Hojabr, Kefford, Richard F., Lau, Loretta M. S., Long, Georgina V., Pickett, Hilda A., Pritchard, Antonia L., Pupo, Gulietta M., Saw, Robyn P. M., Schramm, Sarah-Jane, Shang, Catherine A., Shang, Ping, Spillane, Andrew J., Stretch, Jonathan R., Tembe, Varsha, Thompson, John F., Vilain, Ricardo E., Wilmott, James S., Yang, Jean Y., Hayward, Nicholas K., Mann, Graham J., Scolyer, Richard A., Bartlett, John, Bavi, Prashant, Chadwick, Dianne E., Chan-Seng-Yue, Michelle, Cleary, Sean, Connor, Ashton A., Czajka, Karolina, Denroche, Robert E., Dhani, Neesha C., Eagles, Jenna, Gallinger, Steven, Grant, Robert C., Hedley, David, Hollingsworth, Michael A., Jang, Gun Ho, Johns, Jeremy, Kalimuthu, Sangeetha, Liang, Sheng-Ben, Lungu, Ilinca, Luo, Xuemei, Mbabaali, Faridah, McPherson, Treasa A., Miller, Jessica K., Moore, Malcolm J., Notta, Faiyaz, Pasternack, Danielle, Petersen, Gloria M., Roehrl, Michael H. A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jörg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. R., Bhosle, Shriram G., Birney, Ewan, Borg, Ake, Boyault, Sandrine, Brinkman, Arie B., Brock, Jane E., Broeks, Annegien, Børresen-Dale, Anne-Lise, Caldas, Carlos, Chin, Suet-Feung, Davies, Helen, Desmedt, Christine, Dirix, Luc, Dronov, Serge, Ehinger, Anna, Eyfjord, Jorunn E., Fatima, Aquila, Foekens, John A., Futreal, P. Andrew, Garred, Øystein, Giri, Dilip D., Glodzik, Dominik, Grabau, Dorthe, Hilmarsdottir, Holmfridur, Hooijer, Gerrit K., Jacquemier, Jocelyne, Jang, Se Jin, Jonasson, Jon G., Jonkers, Jos, Kim, Hyung-Yong, King, Tari A., Knappskog, Stian, Kong, Gu, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerød, Anita, Larsimont, Denis, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Ming Ta Michael, Lingjærde, Ole Christian, MacGrogan, Gaetan, Martens, John W. M., O’Meara, Sarah, Pauporté, Iris, Pinder, Sarah, Pivot, Xavier, Provenzano, Elena, Purdie, Colin A., Ramakrishna, Manasa, Ramakrishnan, Kamna, Reis-Filho, Jorge, Richardson, Andrea L., Ringnér, Markus, Rodriguez, Javier Bartolomé, Rodríguez-González, F. Germán, Romieu, Gilles, Salgado, Roberto, Sauer, Torill, Shepherd, Rebecca, Sieuwerts, Anieta M., Simpson, Peter T., Smid, Marcel, Sotiriou, Christos, Span, Paul N., Stefánsson, Ólafur Andri, Stenhouse, Alasdair, Stunnenberg, Henk G., Sweep, Fred, Tan, Benita Kiat Tee, Thomas, Gilles, Thompson, Alastair M., Tommasi, Stefania, Treilleux, Isabelle, Tutt, Andrew, Ueno, Naoto T., Van Laere, Steven, Van Den Eynden, Gert G., Vermeulen, Peter, Viari, Alain, Vincent-Salomon, Anne, Wong, Bernice H., Yates, Lucy, Zou, Xueqing, Van Deurzen, Carolien H. M., Van De Vijver, Marc J., Van’t Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica I., Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Küppers, Ralf, Lenze, Dido, Loeffler, Markus, López, Cristina, Mantovani-Löffler, Luisa, Möller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Trümper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, Von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Jörg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sültmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantù, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-Ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, López-Otín, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O’Donovan, Maria, O’Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavaré, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, Van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al-Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barnholtz-Sloan, Jill, Bathe, Oliver F., Baylin, Stephen B., Benz, Christopher, Berchuck, Andrew, Berrios, Mario, Bigner, Darell, Birrer, Michael, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bosenberg, Marcus, Bowlby, Reanne, Boyd, Jeffrey, Broaddus, Russell R., Brock, Malcolm, Brooks, Denise, Bullman, Susan, Caesar-Johnson, Samantha J., Carey, Thomas E., Carlsen, Rebecca, Cerfolio, Robert, Chandan, Vishal S., Chen, Hsiao-Wei, Cherniack, Andrew D., Chien, Jeremy, Cho, Juok, Chuah, Eric, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G., Curley, Erin, Czerniak, Bogdan, Danilova, Ludmila, Davis, Ian J., Defreitas, Timothy, Demchok, John A., Dhalla, Noreen, Dhir, Rajiv, Doddapaneni, HarshaVardhan, El-Naggar, Adel, Felau, Ina, Ferguson, Martin L., Finocchiaro, Gaetano, Fong, Kwun M., Frazer, Scott, Friedman, William, Fronick, Catrina C., Fulton, Lucinda A., Gabriel, Stacey B., Gao, Jianjiong, Gehlenborg, Nils, Gershenwald, Jeffrey E., Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gomez, Carmen, Govindan, Ramaswamy, Hayes, D. Neil, Hegde, Apurva M., Heiman, David I., Heins, Zachary, Hepperla, Austin J., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Hruban, Ralph H., Hu, Jianhong, Huang, Mei, Huntsman, David, Huse, Jason, Iacobuzio-Donahue, Christine A., Ittmann, Michael, Jayaseelan, Joy C., Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J. M., Juhl, Hartmut, Kang, Koo Jeong, Karlan, Beth, Kasaian, Katayoon, Kebebew, Electron, Kim, Hark Kyun, Korchina, Viktoriya, Kundra, Ritika, Lai, Phillip H., Lander, Eric, Le, Xuan, Lee, Darlene, Levine, Douglas A., Lewis, Lora, Ley, Tim, Li, Haiyan Irene, Lin, Pei, Linehan, W. M., Liu, Fei Fei, Lu, Yiling, Lype, Lisa, Ma, Yussanne, Maglinte, Dennis T., Mardis, Elaine R., Marks, Jeffrey, Marra, Marco A., Matthew, Thomas J., Mayo, Michael, McCune, Karen, Meier, Samuel R., Meng, Shaowu, Mieczkowski, Piotr A., Mikkelsen, Tom, Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morrison, Carl, Mose, Lisle E., Moser, Catherine D., Mungall, Andrew J., Mungall, Karen, Mutch, David, Muzny, Donna M., Myers, Jerome, Newton, Yulia, Noble, Michael S., O’Donnell, Peter, O’Neill, Brian Patrick, Ochoa, Angelica, Park, Joong-Won, Parker, Joel S., Pass, Harvey, Pastore, Alessandro, Pennell, Nathan A., Perou, Charles M., Petrelli, Nicholas, Potapova, Olga, Rader, Janet S., Ramalingam, Suresh, Rathmell, W. Kimryn, Reuter, Victor, Reynolds, Sheila M., Ringel, Matthew, Roach, Jeffrey, Roberts, Lewis R., Robertson, A. Gordon, Sadeghi, Sara, Saller, Charles, Sanchez-Vega, Francisco, Schadendorf, Dirk, Schein, Jacqueline E., Schmidt, Heather K., Schultz, Nikolaus, Seethala, Raja, Senbabaoglu, Yasin, Shelton, Troy, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Shriver, Craig, Signoretti, Sabina, Simons, Janae V., Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J., Smith-McCune, Karen, Socci, Nicholas D., Soloway, Matthew G., Sood, Anil K., Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thompson, R. Houston, Thorne, Leigh B., Tsao, Ming, Umbricht, Christopher, Van Den Berg, David J., Van Meir, Erwin G., Veluvolu, Umadevi, Voet, Douglas, Wang, Linghua, Weinberger, Paul, Weisenberger, Daniel J., Wigle, Dennis, Wilkerson, Matthew D., Wilson, Richard K., Winterhoff, Boris, Wiznerowicz, Maciej, Wong, Tina, Wong, Winghing, Xi, Liu, Yau, Christina, Zhang, Hailei, Zhang, Hongxin, and Zhang, Jiashan

Subjects
article, 3. Good health
Abstract

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5, 6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8, 9; and evaluates a range of more-specialized features of cancer genomes8, 10–18.

128. FOXM1 and polo-like kinase 1 are co-ordinately overexpressed in patients with gastric adenocarcinomas

Author

Dibb, M., Han, N., Choudhury, J., Hayes, S., Valentine, H., West, C., Sharrocks, AD, and Ang, Yeng S.

Subjects
Male, Medicine(all), Gastric adenocarcinoma, Biochemistry, Genetics and Molecular Biology(all), Forkhead Box Protein M1, Cell Cycle Proteins, Forkhead Transcription Factors, Adenocarcinoma, Middle Aged, Protein Serine-Threonine Kinases, PLK1 (Polo-like Kinase 1), Stomach Neoplasms, Proto-Oncogene Proteins, Humans, Female, RNA, Messenger, FOXM1 (Forkhead Protein M1), Research Article, Aged
Abstract

Background Gastric cancers present late in life with advanced disease and carry a poor prognosis. Polo-like Kinase 1 (PLK1) is a mitotic kinase with regulatory functions during G2/M and mitosis in the cell cycle. In mammalian cells, there is an intricate co-regulatory relationship between PLK1 and the forkhead transcription factor FOXM1. It has been demonstrated that individually either PLK1 or FOXM1 expression predicts poorer survival. However, the co-expression of both of these markers in gastric adenocarcinomas has not been reported previously. Methods We aimed to assess the expression of PLK1 and FOXM1 in Gastric adenocarcinomas in a Western Population, to examine whether there is a relationship of PLK1 to FOXM1 in cancer samples. We assess both the protein and mRNA expression in this patient population by Tissue Microarray immunohistochemistry and RT-PCR. Results Immunohistochemistry was performed on biopsy samples from 79 patients with gastric cancer. Paired normal controls were available in 47 patients. FOXM1 expression was significantly associated with gastric adenocarcinoma (p = 0.001). PLK1 and FOXM1 co-expression was demonstrated in 6/8 (75 %) tumours when analysed by RT-PCR. FOXM1 is overexpressed in a large proportion of gastric carcinomas at the protein level and FOXM1 and PLK1 are concomitantly overexpressed at the mRNA level in this cancer type. Conclusions This study has demonstrated that FOXM1 and its target gene PLK1 are coordinately overexpressed in a proportion of gastric adenocarcinomas. This suggests that chemotherapeutic treatments that target this pathway may be of clinical utility.

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129. Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Author

Mourikis, Thanos P., Benedetti, Lorena, Foxall, Elizabeth, Temelkovski, Damjan, Nulsen, Joel, Perner, Juliane, Cereda, Matteo, Lagergren, Jesper, Howell, Michael, Yau, Christopher, Fitzgerald, Rebecca C., Scaffidi, Paola, Ciccarelli, Francesca D., Noorani, Ayesha, Edwards, Paul A. W., Elliott, Rachael Fels, Grehan, Nicola, Nutzinger, Barbara, Hughes, Caitriona, Fidziukiewicz, Elwira, Bornschein, Jan, MacRae, Shona, Crawte, Jason, Northrop, Alex, Contino, Gianmarco, Li, Xiaodun, De La Rue, Rachel, Katz-Summercorn, Annalise, Abbas, Sujath, Loureda, Daniel, O’Donovan, Maria, Miremadi, Ahmad, Malhotra, Shalini, Tripathi, Monika, Tavaré, Simon, Lynch, Andy G., Eldridge, Matthew, Secrier, Maria, Bower, Lawrence, Devonshire, Ginny, Jammula, Sriganesh, Davies, Jim, Crichton, Charles, Carroll, Nick, Safranek, Peter, Hindmarsh, Andrew, Sujendran, Vijayendran, Hayes, Stephen J., Ang, Yeng, Sharrocks, Andrew, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J. E., Hupp, Ted R., Robert O’Neill, J., Tucker, Olga, Beggs, Andrew, Taniere, Philippe, Puig, Sonia, Underwood, Timothy J., Walker, Robert C., Grace, Ben L., Barr, Hugh, Shepherd, Neil, Old, Oliver, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Mahadeva, Ula, Goh, Vicky, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Saunders, John, Lovat, Laurence, Haidry, Rehan, Igali, Laszlo, Scott, Michael, Sothi, Sharmila, Suortamo, Sari, Lishman, Suzy, Hanna, George B., Peters, Christopher J., Moorthy, Krishna, Grabowska, Anna, Turkington, Richard, McManus, Damian, Khoo, David, and Fickling, Will

Subjects
631/67, 13/31, 13/44, 631/67/1504/1477, 38/23, 38/22, 38/77, 38/88, article, 38/90, 631/67/69, 13/109, 3. Good health
Abstract

The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.

130. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Author

Meyerson, William U., Dursi, Lewis Jonathan, Wang, Liang-Bo, Dong, Guanlan, Liang, Wen-Wei, Weerasinghe, Amila, Li, Yize, Kelso, Sean, Wendl, Michael C., Simpson, Jared T., Akbani, Rehan, Anur, Pavana, Bailey, Matthew H., Buchanan, Alex, Chiotti, Kami, Covington, Kyle, Creason, Allison, Ding, Li, Ellrott, Kyle, Fan, Yu, Foltz, Steven, Getz, Gad, Hale, Walker, Haussler, David, Hess, Julian M., Hutter, Carolyn M., Kandoth, Cyriac, Kasaian, Katayoon, Kasapi, Melpomeni, Larson, Dave, Leshchiner, Ignaty, Letaw, John, Ma, Singer, McLellan, Michael D., Men, Yifei, Mills, Gordon B., Niu, Beifang, Peto, Myron, Radenbaugh, Amie, Reynolds, Sheila M., Saksena, Gordon, Sofia, Heidi, Stewart, Chip, Struck, Adam J., Stuart, Joshua M., Wang, Wenyi, Weinstein, John N., Wheeler, David A., Wong, Christopher K., Xi, Liu, Ye, Kai, Bieg, Matthias, Boutros, Paul C., Buchhalter, Ivo, Butler, Adam P., Chen, Ken, Chong, Zechen, Drechsel, Oliver, Jonathan Dursi, Lewis, Eils, Roland, Espiritu, Shadrielle M. G., Fulton, Robert S., Gao, Shengjie, Gelpi, Josep L. L., Gerstein, Mark B., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael C., Hinton, Jonathan, Hu, Taobo, Huang, Vincent, Huang, Yi, Hutter, Barbara, Jones, David R., Jung, Jongsun, Jäger, Natalie, Kim, Hyung-Lae, Kleinheinz, Kortine, Kumar, Sushant, Kumar, Yogesh, Lalansingh, Christopher M., Letunic, Ivica, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Mashl, R. Jay, Menzies, Andrew, Milovanovic, Ana, Nielsen, Morten Muhlig, Ossowski, Stephan, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Perry, Marc D., Puiggròs, Montserrat, Raine, Keiran M., Rheinbay, Esther, Royo, Romina, Sahinalp, S. Cenk, Sarrafi, Iman, Schlesner, Matthias, Stebbings, Lucy, Stobbe, Miranda D., Teague, Jon W., Tiao, Grace, Torrents, David, Wala, Jeremiah A., Wang, Jiayin, Waszak, Sebastian M., Weischenfeldt, Joachim, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yakneen, Sergei, Yamaguchi, Takafumi N., Yellapantula, Venkata D., Yung, Christina K., Zhang, Junjun, Aaltonen, Lauri A., Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J., Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, 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, 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 R., Awadalla, Philip, Aymerich, Marta, Bader, Gary D., Baez-Ortega, Adrian, Bailey, Peter J., 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, 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., Biankin, Andrew V., 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 D. L., 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 J. C., Bruzos, Alicia L., Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H., Busanovich, John, Bustamante, Carlos D., 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, Campbell, Peter J., 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., Chang, David K., Chanock, Stephen J., Chantrill, Lorraine A., Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, 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, 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., Cooke, Susanna L., Cooper, Colin S., Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G., Cordner, Stephen M., Cortés-Ciriano, Isidro, 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, Deshpande, Vikram, Deshwar, Amit G., Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C., Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Shuai, Dinh, Huy Q., Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T., Drapkin, Ronny, Drews, Ruben M., Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J., Dunn, Michael, 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, El-Naggar, Adel, Eldridge, Matthew, Erkek, Serap, Escaramis, Georgia, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E., Faltas, Bishoy M., Fan, Daiming, Faquin, William C., 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., Furuta, Mayuko, Futreal, P. Andrew, Füllgrabe, Anja, Gabriel, Stacey B., Gallinger, Steven, Gambacorti-Passerini, Carlo, Gao, Jianjiong, Garraway, Levi, Garred, Øystein, Garrison, Erik, Garsed, Dale W., Gehlenborg, Nils, George, Joshy, Gerhard, Daniela S., Gerhauser, Clarissa, Gershenwald, Jeffrey E., Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gill, Anthony J., Gill, Pelvender, Giri, Dilip D., Glodzik, Dominik, Gnanapragasam, Vincent J., Goebler, Maria Elisabeth, Goldman, Mary J., Gomez, Carmen, 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, Grimmond, Sean M., Grossman, Robert L., Grundhoff, Adam, Gundem, Gunes, Guo, Qianyun, Gupta, Manaswi, Gupta, Shailja, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haan, David, Haas, Siegfried, Haase, Kerstin, Haber, James E., Habermann, Nina, Haider, Syed, 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, 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., Heins, Zachary, Heisler, Lawrence E., Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J., Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hilmarsdottir, Holmfridur, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hoadley, Katherine A., 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, Hua, Xing, Huang, Kuan-Lin, Huang, Mei, Huang, Mi Ni, Huber, Wolfgang, Hudson, Thomas J., Hummel, Michael, Hung, Jillian A., Huntsman, David, Hupp, Ted R., Huse, Jason, Huska, Matthew R., Hübschmann, Daniel, Iacobuzio-Donahue, Christine A., Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B., Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, S. M. Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose M. G., 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, Jiao, Wei, 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 T. W., Jones, Nic, Jones, Steven J. M., Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Juul, Malene, Juul, Randi Istrup, Juul, Sissel, Kabbe, Rolf, Kahles, Andre, Kahraman, Abdullah, Kaiser, Vera B., Kakavand, Hojabr, Kalimuthu, Sangeetha, Von Kalle, Christof, Kang, Koo Jeong, Karaszi, Katalin, Karlan, Beth, Karlić, Rosa, Karsch, Dennis, Kassahn, Karin S., Katai, Hitoshi, Kato, Mamoru, 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 N. A., Khoo, David, Khoo, Vincent, Khuntikeo, Narong, Khurana, Ekta, Kilpinen, Helena, Kim, Hark Kyun, Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jaegil, Kim, Jihoon, Kim, Jong K., Kim, Youngwook, King, Tari A., Klapper, Wolfram, 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, Kundra, Ritika, Kübler, Kirsten, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H., Laird, Peter W., Lakhani, Sunil R., 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 M. 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Francis, P’ng, Christine, Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Park, Peter J., Parker, Joel S., Parsons, Simon L., Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pearson, John V., Pedamallu, Chandra Sekhar, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A., Perou, Charles M., Petersen, Gloria M., 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, Ramakrishna, Manasa, Ramakrishnan, Kamna, Ramalingam, Suresh, Raphael, Benjamin J., Rathmell, W. 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A., Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C., Rosenwald, Andreas, Rowe, Edward W., 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, Saini, Natalie, Saito-Adachi, Mihoko, 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, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn P. 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M., Van De Vijver, Marc J., Van’t Veer, L., and Von Mering, Christian

Subjects
692/4028/67/69, 706/648/697/129/2043, 631/114/2399, article, 45/23, 139, 631/1647/2217/748, 3. Good health
Abstract

Funder: NCI U24CA211006, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.

131. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Author

Meyerson, William U., Dursi, Lewis Jonathan, Wang, Liang-Bo, Dong, Guanlan, Liang, Wen-Wei, Weerasinghe, Amila, Li, Yize, Kelso, Sean, Wendl, Michael C., Simpson, Jared T., Akbani, Rehan, Anur, Pavana, Bailey, Matthew H., Buchanan, Alex, Chiotti, Kami, Covington, Kyle, Creason, Allison, Ding, Li, Ellrott, Kyle, Fan, Yu, Foltz, Steven, Getz, Gad, Hale, Walker, Haussler, David, Hess, Julian M., Hutter, Carolyn M., Kandoth, Cyriac, Kasaian, Katayoon, Kasapi, Melpomeni, Larson, Dave, Leshchiner, Ignaty, Letaw, John, Ma, Singer, McLellan, Michael D., Men, Yifei, Mills, Gordon B., Niu, Beifang, Peto, Myron, Radenbaugh, Amie, Reynolds, Sheila M., Saksena, Gordon, Sofia, Heidi, Stewart, Chip, Struck, Adam J., Stuart, Joshua M., Wang, Wenyi, Weinstein, John N., Wheeler, David A., Wong, Christopher K., Xi, Liu, Ye, Kai, Bieg, Matthias, Boutros, Paul C., Buchhalter, Ivo, Butler, Adam P., Chen, Ken, Chong, Zechen, Drechsel, Oliver, Jonathan Dursi, Lewis, Eils, Roland, Espiritu, Shadrielle M. G., Fulton, Robert S., Gao, Shengjie, Gelpi, Josep L. L., Gerstein, Mark B., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael C., Hinton, Jonathan, Hu, Taobo, Huang, Vincent, Huang, Yi, Hutter, Barbara, Jones, David R., Jung, Jongsun, Jäger, Natalie, Kim, Hyung-Lae, Kleinheinz, Kortine, Kumar, Sushant, Kumar, Yogesh, Lalansingh, Christopher M., Letunic, Ivica, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Mashl, R. Jay, Menzies, Andrew, Milovanovic, Ana, Nielsen, Morten Muhlig, Ossowski, Stephan, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Perry, Marc D., Puiggròs, Montserrat, Raine, Keiran M., Rheinbay, Esther, Royo, Romina, Sahinalp, S. Cenk, Sarrafi, Iman, Schlesner, Matthias, Stebbings, Lucy, Stobbe, Miranda D., Teague, Jon W., Tiao, Grace, Torrents, David, Wala, Jeremiah A., Wang, Jiayin, Waszak, Sebastian M., Weischenfeldt, Joachim, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yakneen, Sergei, Yamaguchi, Takafumi N., Yellapantula, Venkata D., Yung, Christina K., Zhang, Junjun, Aaltonen, Lauri A., Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J., Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, 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, 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. 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M., Van De Vijver, Marc J., Van’t Veer, L., and Von Mering, Christian

Subjects
692/4028/67/69, 706/648/697/129/2043, 631/114/2399, article, 45/23, 139, 631/1647/2217/748, 3. Good health
Abstract

Funder: NCI U24CA211006, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.

132. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Author

Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, Grimmond, Sean M., Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, and Grimmond, Sean M.

Abstract

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

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133. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Author

Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, Grimmond, Sean M., Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, and Grimmond, Sean M.

Abstract

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

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134. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Author

Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, Grimmond, Sean M., Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, and Grimmond, Sean M.

Abstract

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

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135. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Author

Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, Grimmond, Sean M., Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, and Grimmond, Sean M.

Abstract

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

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136. The burden of Barrett's oesophagus

Author

Britton, James, Mclaughlin, John, Hamdy, Shaheen, and Ang, Yeng

Subjects
616.99, Research Priority Setting, Quality of Life, Barrett's oesophagus
Abstract

Barrett's oesophagus is a well-established and increasingly common precancerous condition which requires long term endoscopic surveillance. Undoubtedly this may impact patients both physically and psychologically. However, very little is known about the true burden of this condition and its care pathways on patients' quality of life. This thesis presents a body of work, in journal format, which aims to give both an in-depth qualitative account of disease impact and quantitative assessment of the prevalence of these factors. Finally, this thesis identifies broader patient centred research uncertainties, which if investigated will hopefully shift the landscape of research in favour of the patient. The chapters presented in this thesis include an introductory literature review which highlights what is currently known, limitations of research to date, and gaps in knowledge concerning BO health related quality of life. The following two chapters (chapters 2 and 3) adopt a mixed method approach (qualitative and quantitative) to assessing BO health related quality of life. These chapters address the impact of symptoms, worry of oesophageal cancer, anxiety, depression, perceptions of cancer risk, experiences of follow up care and patient views on new follow up systems. Chapter 4 then looks at the broader issues facing patients with BO and GORD by asking what are their key future research priorities. This qualitative and quantitative prioritisation process engages both patients and professionals on a level playing. This process culminates in a modified Delphi process to reach a consensus "top 10 research priorities". Chapter 5 begins to assesses the potential benefits of a dedicated BO surveillance service, a top 10 research priority identified in chapter 4. Finally, a discussion chapter brings together the key findings from all 4 journal articles before outlining future research proposals in abstract format.

Published
2020

137. Understanding the regulatory chromatin landscape of oesophageal adenocarcinoma

Author

Rogerson, Connor, Sharrocks, Andrew, and Ang, Yeng

Subjects
616.99, Oesophageal adenocarcinoma, Barrett's oesophagus, HNF4A, GATA6, KLF5, ATAC-seq
Abstract

Oesophageal adenocarcinoma (OAC) is one of the most frequent causes of cancer deaths and yet compared to other common cancers, we know relatively little about the molecular composition of this tumour type. Developmentally, OAC progresses from its precancerous precursor, Barrett's oesophagus (BO). To further our understanding of this cancer we have used open chromatin profiling (ATAC-seq) of normal oesophagus, Barrett's oesophagus and OAC human tissue, and integrated ChIP-seq and RNA-seq of cell-lines to decipher the transcriptional regulatory networks that are operational during OAC development. First by analysing the open chromatin profiles of normal and OAC tissue, we have uncovered an active transcription factor network, which is usually found in primitive intestinal cells during embryonic development, centred on HNF4A and GATA6. By exploring BO ATAC-seq data, we show that this transcription factor network is activated in BO. We also show that HNF4A alone is sufficient to drive chromatin opening and activate a BO-like chromatin signature in normal human oesophageal cells. Second, by focussing on RNA-seq of BO and OAC tissue, we have also identified activation of a cell cycle gene signature during progression from BO to OAC. By integrating ATAC-seq of BO and OAC, we have implicated KLF5 in activating this cell cycle signature. KLF5 binds to cell cycle associated genes specifically in OAC, and patients with high expression of KLF5 target genes have a worse prognosis that those that do not. This thesis has provided a molecular timeline of activation and function of transcription factors, and their target genes, involved in the development of BO and OAC and provided new targets for biomarkers and therapeutics.

Published
2019

141. Chromatin accessibility reveals regulatory pathways in oesophageal adenocarcinoma

Author

Britton, Edward, Sharrocks, Andrew, and Ang, Yeng

Subjects
616.99, transcription factors, human tissue ATAC-seq, chromatin architecture, RNA-seq, transcription regulation, AP1 proteins, ETS proteins, GATA, HNF4a, chromatin accessibility, ATAC-seq, oesophageal adenocarcinoma, oesophageal cancer
Abstract

Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer, which is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood although genomic sequencing studies have identified several genes encoding chromatin remodelling enzymes that are frequently mutated in OAC. This finding is consistent with the knowledge that one important change that occurs in cancer cells is a reprogramming of the chromatin environment which leads to subsequent changes in their transcriptional profile. Here, we have used ATAC-seq to interrogate the chromatin changes that occur in OAC. We demonstrate that there are substantial changes in the regulatory chromatin environment in the cancer cells and using this data we have uncovered an important role for ETS and AP1 transcription factors in driving the changes in gene expression found in OAC cells. Furthermore we have developed the technique of ATAC-seq to allow human tissue biopsies to be processed to identify chromatin changes that occur in real life cancer samples, identifying HNF4a GATA4, GATA6 and FOXA2 as putative regulatory transcription factors in a subset of OAC.

Published
2017

142. Novel FOXM1 transcription factor target genes in oesophageal cancer

Author

Wiseman, Elizabeth Fiona, Sharrocks, Andrew, and Ang, Yeng

Subjects
616.99
Abstract

The prognosis of oesophageal cancer remains poor, with <10% 5-year survival. Delineating the molecular pathogenesis of oesophageal cancer could inform future research into targeted therapies and may uncover novel biomarkers to aid management decisions. As a transcription factor with important roles in the control of cell cycle transcription, FOXM1 regulates cellular proliferation and chromosome stability. FOXM1 is frequently overexpressed in human cancers and this has recently been described in oesophageal adenocarcinoma (OAC) tissues. We have sought to identify novel gene targets of FOXM1 to better understand the molecular pathogenesis of OAC. Using chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) in OE33 OAC cells we investigated the genome-wide DNA binding regions of FOXM1, identifying a shortlist of putative FOXM1 target genes. We then identified those genes with evidence of transcriptional regulation by FOXM1 in primary oesophageal tissue specimens and in OE33 OAC cells subjected to FOXM1-directed RNA interference, using the Nanostring mRNA quantification technique. True direct FOXM1 target genes were defined as those genes that are bound by FOXM1 at their regulatory regions in OE33 cells, significantly downregulated in FOXM1-depleted OE33 cells and significantly overexpressed in primary oesophageal tissues expressing high FOXM1 mRNA levels. We identified the following genes as direct FOXM1 transcriptional targets: CDKN3, CCNB1, CCNF, KIF14, KPNA2, UBE2C, MKI67, GTSE1, TPX2, KIF23, FAM64A, UHRF1, MAD2L1, ANLN, DBF4, ETV4 and ZNF367. All of these genes have functions in cell cycle-related processes, apart from ETV4 and ZNF367 which function as transcriptional activators. The expression levels of ETV4 and UHRF1 were significantly associated with locally advanced disease (advanced T stage) and metastatic disease respectively. Identification of these new FOXM1 transcriptional targets in oesophageal tissues provides further insights into the molecular pathobiology of OAC, by identifying new gene pathways that are upregulated as a result of FOXM1 overexpression in OAC.

Published
2014

143. The FOXM1-PLK1 axis in oesophageal and gastric adenocarcinoma

Author

Dibb, Martyn, Sharrocks, Andrew, and Ang, Yeng

Subjects
616.99, PLK1, FOXM1, Oesophageal Cancer, Cell Cycle, Transcriptional Targets
Abstract

Background: Oesophagogastric cancers generally present late in life with advanced disease and carry a poor prognosis. Few patients receive curative treatment. Polo-like Kinase 1 (PLK1) is a mitotic kinase with regulatory functions at the G2/M cell cycle phase transition. In mammalian cells, PLK1 phosphorylates and activates FOXM1, a forkhead transcription factor at the G2/M cell cycle phase transition. FOXM1 then promotes transcription of multiple gene products, including PLK1 and CCNB1, which then act individually or in complexes to further phosphorylate FOXM1 generating a positive feedback loop driving the cell into M phase. Aims: We aimed to assess the expression of PLK1 and FOXM1 in oesophageal and gastric cancer patients. Secondly we aimed to investigate the expression and inter- relationship of PLK1 and FOXM1 in oesophageal cell lines during the cell cycle. Results: FOXM1 and PLK1 are expressed in oesophageal cell lines and demonstrate cross-regulatory interactions. Inhibition of PLK1 leads to the decreased expression of FOXM1 and it’s target gene in oesophageal cell lines. FOXM1 and PLK1 are also concomitantly overexpressed in a large proportion of oesophageal and gastric carcinoma’s at both the protein and mRNA level. Other FOXM1 target genes including, CCBN1, AURKB and CKS1 are co-expressed in a similar manner. In a homogenous cohort of patients who underwent surgery, the expression of PLK1 and AURKB was prognostic for overall survival. Conclusions: This study has demonstrated that FOXM1 and a number of target genes including PLK1 are coordinately expressed in a proportion of oesophageal and gastric carcinomas. This suggests that chemotherapeutic treatments that target this pathway may be of clinical utility.

Published
2013

144. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score

Author

Marco Carbone, Alessandra Nardi, Steve Flack, Guido Carpino, Nikoletta Varvaropoulou, Caius Gavrila, Ann Spicer, Jonathan Badrock, Francesca Bernuzzi, Vincenzo Cardinale, Holly F Ainsworth, Michael A Heneghan, Douglas Thorburn, Andrew Bathgate, Rebecca Jones, James M Neuberger, Pier Maria Battezzati, Massimo Zuin, Simon Taylor-Robinson, Maria F Donato, John Kirby, Robert Mitchell-Thain, Annarosa Floreani, Fotios Sampaziotis, Luigi Muratori, Domenico Alvaro, Marco Marzioni, Luca Miele, Fabio Marra, Edoardo Giannini, Eugenio Gaudio, Vincenzo Ronca, Giulia Bonato, Laura Cristoferi, Federica Malinverno, Alessio Gerussi, Deborah D Stocken, Heather J Cordell, Gideon M Hirschfield, Graeme J Alexander, Richard N Sandford, David E Jones, Pietro Invernizzi, George F Mells, Caradog Thomas, Meshbah Rahman, Tom Yapp, Chin Lye Ch'ng, Melanie Harrison, Richard Sturgess, Roman Galaska, Chris Healey, Jessica Whiteman, Marek Czaijkowski, Catherine Gray, Anton Gunasekera, Pranab Gyawli, Purushothaman Premchand, Steven Mann, Keith Elliott, Kapil Kapur, Alan Watson, Graham Foster, Paul Trembling, Javaid Subhani, Rory Harvey, Roger McCorry, Carolyn Adgey, Lucie Hobson, Caroline Mulvaney-Jones, Richard Evans, Thiriloganathan Mathialahan, David Ramanaden, Jaber Gasem, Greta Van Duyvenvoorde, Christopher Shorrock, Katie Seward, Paul Southern, Jeremy Tibble, Ruth Penn, David Gorard, Jane Maiden, Rose Damant, Altaf Palegwala, Susan Jones, Graeme Alexander, George Mells, Richard Sandford, Sunil Dolwani, Martin Prince, Valeria Silvestre, Matthew Foxton, Eleanor Dungca, Harriet Mitchison, Natalie Wheatley, Ian Gooding, Helen Doyle, Mazn Karmo, Melanie Kent, Sushma Saksena, Delyth Braim, Minesh Patel, Susan Lord, Roland Ede, Alison Paton, Andrew Austin, Nicola Lancaster, Joanna Sayer, Andrew Gibbins, Karen Hogben, Chris Hovell, Neil Fisher, Martyn Carter, Konrad Koss, Janine Musselwhite, Florin Muscariu, Andrzej Piotreowicz, Alexandra McKay, Charles Grimley, David Neal, Lai Ting Tan, Guan Lim, Jacqueline Brighton, Carole Foale, Aftab Ala, Athar Saeed, Kerry Flahive, Gordon Wood, Paula Townshend, Chris Ford, Jonathan Brown, Jean Kordula, Jane Bowles, Mark Wilkinson, Caroline Palmer, John Ramage, Harriet Gordon, James Featherstone, Jo Ridpath, Theodore Ngatchu, Sass Levi, Syed Shaukat, Joy Sadeghian, Ray Shidrawi, Bronwen Williams, George Abouda, Sarah Jones, Claire Duggan, Abigail Hynes, Mark Narain, Ian Rees, Imroz Salam, Mary Crossey, Ashley Brown, Carolyn MacNicol, Simon Williams, Elva Wilhelmsen, Paul Banim, Parizade Raymode, Andrew Chilton, Debasish Das, Hye-Jeong Lee, Howard Curtis, Michael Heneghan, Markus Gess, Emma Durant, IM Drake, Rebecca Bishop, Mervyn Davies, Mark Aldersley, Noma Ncube, Alistair McNair, Raj Srirajaskanthan, Sambit Sen, Rebecca Casey, George Bird, Mike Mendall, Caroline Cowley, Adrian Barnardo, Paul Kitchen, Kevin Yoong, Kelly Amore, Dawn Sirdefield, Jacky Orpe, Ray Mathew, George MacFaul, Aruna Wrigth, Amir Shah, Chris Evans, Janie Keggans, Bridget Bird, Gwen Baxter, Subrata Saha, Katharine Pollock, Maggie Hughes, Peter Bramley, Emma Grieve, Karin Young, Andrew Fraser, Ashis Mukhopadhya, Kate Ocker, Peter Mills, Francis Hines, Chris Shallcross, Joy Wilkins, Leonie Grellier, Stewart Campbell, Kirsty Martin, Caron Innes, Alan Shepherd, Simon Rushbrook, Talal Valliani, Robert Przemioslo, Helen Fairlamb, Chris Macdonald, Anne Eastick, Jane Metcalf, Elizabeth Tanqueray, Udi Shmueli, Becky Holbrook, Andrew Davis, Julie Browning, Asifabbas Naqvi, Kirsten Walker, Tom Lee, Juliette Verheyden, Susan Slininger, Stephen D Ryder, Roger Chapman, Jane Collier, Denise O'Donnell, Lizzie Stafford, Kate Williamson, Linda Kent, Howard Klass, Mary Ninkovic, Linda March, Matthew Cramp, Diane Simpson, Christine Dickson, Nicholas Sharer, Maria Hayes, Patrick Goggin, Mary Quinne, Sallyanne Pearson, Barbara Hoeroldt, Linda Jones, Alice Wright, Jonathan Booth, Alison Loftus, George Lipscomb, Hannah Dewhurst, Emma Gunter, Earl Williams, Anna Fouracres, Liz Farrington, Lyn Graves, Hyder Hussaini, Bill Stableforth, Suzie Marriott, Reuben Ayres, Marina Leoni, Andrew Burroughs, Eileen Marshall, David Tyrer, Kate Martin, Martin Lombard, Imran Patanwala, Lola Dali-Kemmery, Victoria Lambourne, Julia Maltby, Samir Vyas, Julie Colley, Bal Shinder, Saket Singhal, Jayne Jones, Marisa Mills, Dermot Gleeson, Mandy Carnahan, Jeff Butterworth, Kerenza Boulton, Natalie Taylor, Keith George, Tim Harding, Julie Tregonning, Andrew Douglass, Carly Brown, Gayle Clifford, Simon Panter, Denise Gocher, Jeremy Shearman, Gary Bray, Maria Hamilton, Graham Butcher, Daniel Forton, John Mclindon, Janette Curtis, Debashis Das, Tracey Shewan, Matthew Cowan, Gregory Whatley, Mariam Nasseri, Bob Grover, Nurani Sivaramakrishnan, Samantha Ducker, Kathryn Houghton, David Jones, Laura Griffiths, Sherill Tripoli, Maxton Pitcher, Ervin Shpuza, Nikki White, Deb Ghosh, Andrew Douds, Marie Green, Matthew Brookes, Lourdes Cumlat, Voi Shim Wong, Karen Warner, Kimberley Netherton, Adtya Mandal, Snjiv Jain, Hemant Gupta, Pradeep Sanghi, Steve Pereira, James Neuberger, Bridget Gunson, Gideon Hirschfield, Reina Teegan Lim, Susan Gallagher, Darren Clement, Alison Brind, Gill Watts, Mcdonald Mupudzi, Mark Wright, Jane Gitahi, Fiona Gordon, Denis Gocher, Esther Unitt, Hilary Pateman, Sally Batham, Toby Delahooke, Allister Grant, Jill Conder, Andrew Higham, Mark Cox, Lynn O'Donohoe, Lynn Currie, Alistair King, Metod Oblak, Carole Collins, Simon Whalley, Marie Quinn, Yolanda Baird, Isobel Amey, Jocelyn Fraser, Andy Li, Donna Cotterill, Andrew Bell, Amit Singhal, Ian Gee, Sandra Greer, Yeng Ang, Rupert Ransford, Joanna Allison, James Gotto, Simon Dyer, Helen Sweeting, Charles Millson, Giancarlo Labbadia, Maria Consiglia Bragazzi, Pietro Andreone, Francesco Azzaroli, Andrea Galli, Mirko Tarocchi, Antonio Gasbarrini, Antonio Grieco, Giuseppe Marrone, Maria Francesca Donato, Luca Valenti, Luca Maroni, Cristina Rigamonti, Antonino Picciotto, Carbone, M, Nardi, A, Flack, S, Carpino, G, Varvaropoulou, N, Gavrila, C, Spicer, A, Badrock, J, Bernuzzi, F, Cardinale, V, Ainsworth, H, Heneghan, M, Thorburn, D, Bathgate, A, Jones, R, Neuberger, J, Battezzati, P, Zuin, M, Taylor-Robinson, S, Donato, M, Kirby, J, Mitchell-Thain, R, Floreani, A, Sampaziotis, F, Muratori, L, Alvaro, D, Marzioni, M, Miele, L, Marra, F, Giannini, E, Gaudio, E, Ronca, V, Bonato, G, Cristoferi, L, Malinverno, F, Gerussi, A, Stocken, D, Cordell, H, Hirschfield, G, Alexander, G, Sandford, R, Jones, D, Invernizzi, P, Mells, G, Thomas, C, Rahman, M, Yapp, T, Lye Ch'ng, C, Harrison, M, Sturgess, R, Galaska, R, Healey, C, Whiteman, J, Czaijkowski, M, Gray, C, Gunasekera, A, Gyawli, P, Premchand, P, Mann, S, Elliott, K, Kapur, K, Watson, A, Foster, G, Trembling, P, Subhani, J, Harvey, R, Mccorry, R, Adgey, C, Hobson, L, Mulvaney-Jones, C, Evans, R, Mathialahan, T, Ramanaden, D, Gasem, J, Van Duyvenvoorde, G, Shorrock, C, Seward, K, Southern, P, Tibble, J, Penn, R, Gorard, D, Maiden, J, Damant, R, Palegwala, A, Jones, S, Dolwani, S, Prince, M, Silvestre, V, Foxton, M, Dungca, E, Mitchison, H, Wheatley, N, Gooding, I, Doyle, H, Karmo, M, Kent, M, Saksena, S, Braim, D, Patel, M, Lord, S, Ede, R, Paton, A, Austin, A, Lancaster, N, Sayer, J, Gibbins, A, Hogben, K, Hovell, C, Fisher, N, Carter, M, Koss, K, Musselwhite, J, Muscariu, F, Piotreowicz, A, Mckay, A, Grimley, C, Neal, D, Ting Tan, L, Lim, G, Brighton, J, Foale, C, Ala, A, Saeed, A, Flahive, K, Wood, G, Townshend, P, Ford, C, Brown, J, Kordula, J, Bowles, J, Wilkinson, M, Palmer, C, Ramage, J, Gordon, H, Featherstone, J, Ridpath, J, Ngatchu, T, Levi, S, Shaukat, S, Sadeghian, J, Shidrawi, R, Williams, B, Abouda, G, Duggan, C, Hynes, A, Narain, M, Rees, I, Salam, I, Crossey, M, Brown, A, Macnicol, C, Williams, S, Wilhelmsen, E, Banim, P, Raymode, P, Chilton, A, Das, D, Lee, H, Curtis, H, Gess, M, Durant, E, Drake, I, Bishop, R, Davies, M, Aldersley, M, Ncube, N, Mcnair, A, Srirajaskanthan, R, Sen, S, Casey, R, Bird, G, Mendall, M, Cowley, C, Barnardo, A, Kitchen, P, Yoong, K, Amore, K, Sirdefield, D, Orpe, J, Mathew, R, Macfaul, G, Wrigth, A, Shah, A, Evans, C, Keggans, J, Bird, B, Baxter, G, Saha, S, Pollock, K, Hughes, M, Bramley, P, Grieve, E, Young, K, Fraser, A, Mukhopadhya, A, Ocker, K, Mills, P, Hines, F, Shallcross, C, Wilkins, J, Grellier, L, Campbell, S, Martin, K, Innes, C, Shepherd, A, Rushbrook, S, Valliani, T, Przemioslo, R, Fairlamb, H, Macdonald, C, Eastick, A, Metcalf, J, Tanqueray, E, Shmueli, U, Holbrook, B, Davis, A, Browning, J, Naqvi, A, Walker, K, Lee, T, Verheyden, J, Slininger, S, Ryder, S, Chapman, R, Collier, J, O'Donnell, D, Stafford, L, Williamson, K, Kent, L, Klass, H, Ninkovic, M, March, L, Cramp, M, Simpson, D, Dickson, C, Sharer, N, Hayes, M, Goggin, P, Quinne, M, Pearson, S, Hoeroldt, B, Jones, L, Wright, A, Booth, J, Loftus, A, Lipscomb, G, Dewhurst, H, Gunter, E, Williams, E, Fouracres, A, Farrington, L, Graves, L, Hussaini, H, Stableforth, B, Marriott, S, Ayres, R, Leoni, M, Burroughs, A, Marshall, E, Tyrer, D, Lombard, M, Patanwala, I, Dali-Kemmery, L, Lambourne, V, Maltby, J, Vyas, S, Colley, J, Shinder, B, Singhal, S, Jones, J, Mills, M, Gleeson, D, Carnahan, M, Butterworth, J, Boulton, K, Taylor, N, George, K, Harding, T, Tregonning, J, Douglass, A, Brown, C, Clifford, G, Panter, S, Gocher, D, Shearman, J, Bray, G, Hamilton, M, Butcher, G, Forton, D, Mclindon, J, Curtis, J, Shewan, T, Cowan, M, Whatley, G, Nasseri, M, Grover, B, Sivaramakrishnan, N, Ducker, S, Houghton, K, Griffiths, L, Tripoli, S, Pitcher, M, Shpuza, E, White, N, Ghosh, D, Douds, A, Green, M, Brookes, M, Cumlat, L, Wong, V, Warner, K, Netherton, K, Mandal, A, Jain, S, Gupta, H, Sanghi, P, Pereira, S, Gunson, B, Lim, R, Gallagher, S, Clement, D, Brind, A, Watts, G, Mupudzi, M, Wright, M, Gitahi, J, Gordon, F, Unitt, E, Pateman, H, Batham, S, Delahooke, T, Grant, A, Conder, J, Higham, A, Cox, M, O'Donohoe, L, Currie, L, King, A, Oblak, M, Collins, C, Whalley, S, Quinn, M, Baird, Y, Amey, I, Fraser, J, Li, A, Cotterill, D, Bell, A, Singhal, A, Gee, I, Greer, S, Ang, Y, Ransford, R, Allison, J, Gotto, J, Dyer, S, Sweeting, H, Millson, C, Labbadia, G, Bragazzi, M, Andreone, P, Azzaroli, F, Galli, A, Tarocchi, M, Gasbarrini, A, Grieco, A, Marrone, G, Valenti, L, Maroni, L, Rigamonti, C, Picciotto, A, Sampaziotis, Fotios [0000-0003-0812-7586], Sandford, Richard [0000-0002-7437-0560], Apollo - University of Cambridge Repository, Carbone, Marco, Nardi, Alessandra, Flack, Steve, Carpino, Guido, Varvaropoulou, Nikoletta, Gavrila, Caiu, Spicer, Ann, Badrock, Jonathan, Bernuzzi, Francesca, Cardinale, Vincenzo, Ainsworth, Holly F, Heneghan, Michael A, Thorburn, Dougla, Bathgate, Andrew, Jones, Rebecca, Neuberger, James M, Battezzati, Pier Maria, Zuin, Massimo, Taylor-Robinson, Simon, Donato, Maria F, Kirby, John, Mitchell-Thain, Robert, Floreani, Annarosa, Sampaziotis, Fotio, Muratori, Luigi, Alvaro, Domenico, Marzioni, Marco, Miele, Luca, Marra, Fabio, Giannini, Edoardo, Gaudio, Eugenio, Ronca, Vincenzo, Bonato, Giulia, Cristoferi, Laura, Malinverno, Federica, Gerussi, Alessio, Stocken, Deborah D, Cordell, Heather J, Hirschfield, Gideon M, Alexander, Graeme J, Sandford, Richard N, Jones, David E, Invernizzi, Pietro, Mells, George F, Thomas, Caradog, Rahman, Meshbah, Yapp, Tom, Lye Ch'ng, Chin, Harrison, Melanie, Sturgess, Richard, Galaska, Roman, Healey, Chri, Whiteman, Jessica, Czaijkowski, Marek, Gray, Catherine, Gunasekera, Anton, Gyawli, Pranab, Premchand, Purushothaman, Mann, Steven, Elliott, Keith, Kapur, Kapil, Watson, Alan, Foster, Graham, Trembling, Paul, Subhani, Javaid, Harvey, Rory, McCorry, Roger, Adgey, Carolyn, Hobson, Lucie, Mulvaney-Jones, Caroline, Evans, Richard, Mathialahan, Thiriloganathan, Ramanaden, David, Gasem, Jaber, Van Duyvenvoorde, Greta, Shorrock, Christopher, Seward, Katie, Southern, Paul, Tibble, Jeremy, Penn, Ruth, Gorard, David, Maiden, Jane, Damant, Rose, Palegwala, Altaf, Jones, Susan, Alexander, Graeme, Mells, George, Sandford, Richard, Dolwani, Sunil, Prince, Martin, Silvestre, Valeria, Foxton, Matthew, Dungca, Eleanor, Mitchison, Harriet, Wheatley, Natalie, Gooding, Ian, Doyle, Helen, Karmo, Mazn, Kent, Melanie, Saksena, Sushma, Braim, Delyth, Patel, Minesh, Lord, Susan, Ede, Roland, Paton, Alison, Austin, Andrew, Lancaster, Nicola, Sayer, Joanna, Gibbins, Andrew, Hogben, Karen, Hovell, Chri, Fisher, Neil, Carter, Martyn, Koss, Konrad, Musselwhite, Janine, Muscariu, Florin, Piotreowicz, Andrzej, McKay, Alexandra, Grimley, Charle, Neal, David, Ting Tan, Lai, Lim, Guan, Brighton, Jacqueline, Foale, Carole, Ala, Aftab, Saeed, Athar, Flahive, Kerry, Wood, Gordon, Townshend, Paula, Ford, Chri, Brown, Jonathan, Kordula, Jean, Bowles, Jane, Wilkinson, Mark, Palmer, Caroline, Ramage, John, Gordon, Harriet, Featherstone, Jame, Ridpath, Jo, Ngatchu, Theodore, Levi, Sa, Shaukat, Syed, Sadeghian, Joy, Shidrawi, Ray, Williams, Bronwen, Abouda, George, Jones, Sarah, Duggan, Claire, Hynes, Abigail, Narain, Mark, Rees, Ian, Salam, Imroz, Crossey, Mary, Brown, Ashley, MacNicol, Carolyn, Williams, Simon, Wilhelmsen, Elva, Banim, Paul, Raymode, Parizade, Chilton, Andrew, Das, Debasish, Lee, Hye-Jeong, Curtis, Howard, Heneghan, Michael, Gess, Marku, Durant, Emma, Drake, I.M., Bishop, Rebecca, Davies, Mervyn, Aldersley, Mark, Ncube, Noma, McNair, Alistair, Srirajaskanthan, Raj, Sen, Sambit, Casey, Rebecca, Bird, George, Mendall, Mike, Cowley, Caroline, Barnardo, Adrian, Kitchen, Paul, Yoong, Kevin, Amore, Kelly, Sirdefield, Dawn, Orpe, Jacky, Mathew, Ray, MacFaul, George, Wrigth, Aruna, Shah, Amir, Evans, Chri, Keggans, Janie, Bird, Bridget, Baxter, Gwen, Saha, Subrata, Pollock, Katharine, Hughes, Maggie, Bramley, Peter, Grieve, Emma, Young, Karin, Fraser, Andrew, Mukhopadhya, Ashi, Ocker, Kate, Mills, Peter, Hines, Franci, Shallcross, Chri, Wilkins, Joy, Grellier, Leonie, Campbell, Stewart, Martin, Kirsty, Innes, Caron, Shepherd, Alan, Rushbrook, Simon, Valliani, Talal, Przemioslo, Robert, Fairlamb, Helen, Macdonald, Chri, Eastick, Anne, Metcalf, Jane, Tanqueray, Elizabeth, Shmueli, Udi, Holbrook, Becky, Davis, Andrew, Browning, Julie, Naqvi, Asifabba, Walker, Kirsten, Lee, Tom, Verheyden, Juliette, Slininger, Susan, Ryder, Stephen D, Chapman, Roger, Collier, Jane, O'Donnell, Denise, Stafford, Lizzie, Williamson, Kate, Kent, Linda, Klass, Howard, Ninkovic, Mary, March, Linda, Cramp, Matthew, Simpson, Diane, Dickson, Christine, Sharer, Nichola, Hayes, Maria, Goggin, Patrick, Quinne, Mary, Pearson, Sallyanne, Hoeroldt, Barbara, Jones, Linda, Wright, Alice, Booth, Jonathan, Loftus, Alison, Lipscomb, George, Dewhurst, Hannah, Gunter, Emma, Williams, Earl, Fouracres, Anna, Farrington, Liz, Graves, Lyn, Hussaini, Hyder, Stableforth, Bill, Marriott, Suzie, Ayres, Reuben, Leoni, Marina, Burroughs, Andrew, Marshall, Eileen, Tyrer, David, Martin, Kate, Lombard, Martin, Patanwala, Imran, Dali-Kemmery, Lola, Lambourne, Victoria, Maltby, Julia, Vyas, Samir, Colley, Julie, Shinder, Bal, Singhal, Saket, Jones, Jayne, Mills, Marisa, Gleeson, Dermot, Carnahan, Mandy, Butterworth, Jeff, Boulton, Kerenza, Taylor, Natalie, George, Keith, Harding, Tim, Tregonning, Julie, Douglass, Andrew, Brown, Carly, Clifford, Gayle, Panter, Simon, Gocher, Denise, Shearman, Jeremy, Bray, Gary, Hamilton, Maria, Butcher, Graham, Forton, Daniel, Mclindon, John, Curtis, Janette, Das, Debashi, Shewan, Tracey, Cowan, Matthew, Whatley, Gregory, Nasseri, Mariam, Grover, Bob, Sivaramakrishnan, Nurani, Ducker, Samantha, Houghton, Kathryn, Jones, David, Griffiths, Laura, Tripoli, Sherill, Pitcher, Maxton, Shpuza, Ervin, White, Nikki, Ghosh, Deb, Douds, Andrew, Green, Marie, Brookes, Matthew, Cumlat, Lourde, Wong, Voi Shim, Warner, Karen, Netherton, Kimberley, Mandal, Adtya, Jain, Snjiv, Gupta, Hemant, Sanghi, Pradeep, Pereira, Steve, Neuberger, Jame, Gunson, Bridget, Hirschfield, Gideon, Lim, Reina Teegan, Gallagher, Susan, Clement, Darren, Brind, Alison, Watts, Gill, Mupudzi, Mcdonald, Wright, Mark, Gitahi, Jane, Gordon, Fiona, Gocher, Deni, Unitt, Esther, Pateman, Hilary, Batham, Sally, Delahooke, Toby, Grant, Allister, Conder, Jill, Higham, Andrew, Cox, Mark, O'Donohoe, Lynn, Currie, Lynn, King, Alistair, Oblak, Metod, Collins, Carole, Whalley, Simon, Quinn, Marie, Baird, Yolanda, Amey, Isobel, Fraser, Jocelyn, Li, Andy, Cotterill, Donna, Bell, Andrew, Singhal, Amit, Gee, Ian, Greer, Sandra, Ang, Yeng, Ransford, Rupert, Allison, Joanna, Gotto, Jame, Dyer, Simon, Sweeting, Helen, Millson, Charle, Labbadia, Giancarlo, Bragazzi, Maria Consiglia, Andreone, Pietro, Azzaroli, Francesco, Galli, Andrea, Tarocchi, Mirko, Gasbarrini, Antonio, Grieco, Antonio, Marrone, Giuseppe, Donato, Maria Francesca, Valenti, Luca, Maroni, Luca, Rigamonti, Cristina, Picciotto, Antonino, and Medical Research Council (MRC)

Subjects
Male, Cholagogues and Choleretics, Cirrhosis, medicine.medical_treatment, PROGRESSION, Liver transplantation, PHENOTYPE, Gastroenterology, UDCA, 0302 clinical medicine, Primary biliary cirrhosis, Risk Factors, Medicine, Age of Onset, CIRRHOSIS, TREE, OUTCOMES, Settore MED/12 - Gastroenterologia, medicine.diagnostic_test, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Area under the curve, URSODIOL, Middle Aged, Ursodeoxycholic acid, Treatment Outcome, Primary biliary cholangitis, ursodeoxycholic acid, 030220 oncology & carcinogenesis, Liver biopsy, Area Under Curve, 030211 gastroenterology & hepatology, Female, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, CONTROLLED-TRIAL, Hepatology, Decision Support Techniques, Time-to-Treatment, Biliary injury, 03 medical and health sciences, Internal medicine, Humans, Transaminases, Science & Technology, Gastroenterology & Hepatology, Italian PBC Study Group and the UK–PBC Consortium, business.industry, Bilirubin, medicine.disease, Alkaline Phosphatase, ROC Curve, CELLS, Linear Models, business
Abstract

Background: Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters. Methods: We did logistic regression analysis of pretreatment variables in a discovery cohort of patients in the UK with primary biliary cholangitis to derive the best-fitting model of UDCA response, defined as alkaline phosphatase less than 1·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples. Findings: 2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p

Published
2018
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145. Author Correction: Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1.

Author

Garcia, Edwin, Hayden, Annette, Birts, Charles, Britton, Edward, Rogerson, Connor, Bleaney, Christopher W., Cowie, Andrew, Pickard, Karen, Mellone, Massimiliano, Choh, Clarisa, Derouet, Mathieu, Duriez, Patrick, Noble, Fergus, White, Michael J., Primrose, John N., Strefford, Jonathan C., Rose-Zerilli, Matthew, Thomas, Gareth J., Ang, Yeng, and Sharrocks, Andrew D.

Abstract

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper [ABSTRACT FROM AUTHOR]

Published
2019
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146. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

Author

Cordell, Heather J., Younghun, Han, Mells, George F., Yafang, Li, Hirschfield, Gideon M., Greene, Casey S., Gang, Xie, Juran 7, Brian D., Dakai Zhu, 2, Qian 2, David C., Floyd, James A. B., Morley, Katherine I., Daniele Prati 11, Ana Lleo 12, Daniele, Cusi, Eric Gershwin 15, M., Anderson 8, Carl A., Lazaridis 7, Konstantinos N., Pietro, Invernizzi, Seldin 15, Michael F., Sandford, Richard N., Amos 2, Christopher I., Siminovitch, Katherine A., Schlicht 7, Erik M., Craig Lammert, 7, Atkinson 19, Elizabeth J., Chan 19, Landon L., Mariza de Andrade 19, Tobias Balschun 20, Mason 21, Andrew L., Myers 22, Robert P., Jinyi Zhang 23, Piotr Milkiewicz 24, Jia Qu 25, Odin 26, Joseph A., Luketic 27, Velimir A., Bacon 28, Bruce R., Bodenheimer Jr 29, Henry C., Valentina Liakina 30, Catherine Vincent 31, Cynthia Levy 32, Gregersen, Peter K., Almasio, 33 Piero L., Domenico Alvaro 35, Pietro Andreone 36, Angelo Andriulli 37, Cristina Barlassina 38, Pier Maria Battezzati 39, Antonio Benedetti 40, Francesca Bernuzzi 41, Ilaria Bianchi 41, Maria Consiglia Bragazzi 42, Maurizia Brunetto 43, Savino Bruno 41, Giovanni Casella 44, Barbara Coco 43, Agostino Colli 45, Massimo Colombo 46, Silvia Colombo 47, Carmela Cursaro 36, Lory Saveria Croce, ` 48, Andrea Crosignani 39, Maria Francesca Donato 46, Gianfranco Elia 49, Luca Fabris 50, Carlo Ferrari 49, Annarosa Floreani 51, Barbara Foglieni 11, Rosanna Fontana 37, Galli, Andrea, Roberta Lazzari 51, Fabio Macaluso 34, Federica Malinverno 46, Marra, Fabio, Marco Marzioni 40, Alberto Mattalia 54, Renzo Montanari 55, Lorenzo Morini 56, Filomena Morisco 57, Mousa Hani S., 41, Luigi Muratori 36, Paolo Muratori 36, Niro 37, Grazia A., Palmieri 58, Vincenzo O., Antonio Picciotto 59, Mauro Podda 41, Piero Portincasa 58, Vincenzo Ronca 41, Floriano Rosina 60, Sonia Rossi 41, Ilaria Sogno 41, Giancarlo Spinzi 61, Marta Spreafico 11, Mario, Strazzabosco, Sonia Tarallo 60, Tarocchi, Mirko, Claudio Tiribelli 48, Pierluigi Toniutto 64, Maria Vinci 65, Massimo, Zuin, Chin Lye Ch’ng, Mesbah Rahman 68, Tom Yapp 69, Richard Sturgess 70, Christopher Healey 71, Marek, Czajkowski, Anton, Gunasekera, Pranab Gyawali 77, Purushothaman Premchand 78, Kapil Kapur 79, Richard Marley 80, Graham Foster 80, Alan Watson 81, Aruna Dias 82, Javaid Subhani 83, Rory Harvey 84, Roger McCorry 85, David Ramanaden 86, Jaber Gasem 87, Richard Evans 88, Thiriloganathan Mathialahan 89, Christopher Shorrock 90, George Lipscomb 91, Paul Southern 92, Jeremy Tibble 93, David, Gorard, Altaf Palegwala 98, Susan, Jones, Marco Carbone 101, Mohamed Dawwas 101, Graeme Alexander 101, Sunil, Dolwani, Martin Prince 104, Matthew Foxton 105, David Elphick 106, Harriet Mitchison 107, Ian Gooding 108, Mazn Karmo 109, Sushma, Saksena, Mike, Mendall, Minesh, Patel, Roland, Ede, Andrew Austin 119, Joanna, Sayer, Lorraine Hankey 122, Christopher Hovell 122, Neil Fisher 123, Martyn, Carter, Konrad Koss 126, Andrzej, Piotrowicz, Charles, Grimley, David, Neal, Guan Lim 135, Sass, Levi, Aftab Ala 138, Andrea Broad 139, Athar Saeed 139, Gordon Wood 140, Jonathan, Brown, Mark, Wilkinson, Harriet Gordon 145, John Ramage 146, Jo Ridpath 147, Theodore, Ngatchu, Bob Grover 151, Syed Shaukat 152, Ray Shidrawi 153, George, Abouda, Faiz Ali 156, Ian Rees 157, Imroz Salam 158, Mark Narain 159, Ashley, Brown, Simon Taylor Robinson 162, Simon Williams 163, Leonie Grellier 164, Paul Banim 165, Debasish Das 166, Andrew Chilton 166, Michael Heneghan 167, Howard, Curtis, Markus Gess 170, Ian, Drake, Mark, Aldersley, Mervyn, Davies, Rebecca, Jones, Alastair McNair 175, Raj Srirajaskanthan 176, Maxton, Pitcher, Sambit Sen 179, George, Bird, Adrian Barnardo 182, Paul Kitchen 182, Kevin Yoong 183, Oza, Chirag, Nurani Sivaramakrishnan 186, George MacFaul 187, David Jones 188, Amir Shah 189, Chris Evans 190, Subrata Saha 191, Katharine, Pollock, Peter, Bramley, Ashis, Mukhopadhya, Andrew, Fraser, Peter, Mills, Christopher, Shallcross, Stewart, Campbell, Andrew, Bathgate, Alan Shepherd 213, John Dillon 214, Simon Rushbrook 215, Robert Przemioslo 216 Christopher Macdonald, Jane, Metcalf, Udi Shmueli 221, Andrew, Davis, Asifabbas, Naqvi, Tom, Lee, Ryder, Stephen D., Jane Collier 231, Howard, Klass, Mary, Ninkovic, Matthew Cramp 238, Nicholas Sharer 239, Richard Aspinall 240, Patrick Goggin 240, Deb, Ghosh, Andrew Douds 243, Barbara Hoeroldt 244, Jonathan Booth 245, Earl Williams 246, Hyder Hussaini 247, William Stableforth 247, Reuben Ayres 248, Douglas Thorburn 249, Eileen Marshall 249, Andrew Burroughs 249, Steven, Mann, Martin Lombard 252, Paul Richardson 252, Imran Patanwala 252, Julia Maltby 253, Matthew Brookes 254, Ray, Mathew, Samir Vyas 257, Saket Singhal 258, Dermot, Gleeson, Sharat, Misra, Jeff, Butterworth, Keith George 265, Tim, Harding, Andrew, Douglass, Simon Panter 270, Jeremy Shearman 271, Gary Bray 272, Graham, Butcher, Daniel Forton 275, John, Mclindon, Matthew Cowan 279, Gregory Whatley 280, Aditya, Mandal, Hemant, Gupta, Pradeep, Sanghi, Sanjiv Jain 283, Steve Pereira 284, Geeta Prasad 285, Gill Watts 285, Mark Wright 286, James Neuberger 287, Fiona Gordon 288, Esther Unitt 289, Allister, Grant, Toby, Delahooke, Andrew Higham 293, Alison Brind 294, Mark Cox 295, Subramaniam Ramakrishnan 296, Alistair, King, Carole Collins 300, Simon, Whalley, Andy Li 303, Jocelyn Fraser 304, Andrew Bell 305, Voi Shim Wong 306, Amit, Singhal, Ian, Gee, Yeng Ang 312, Rupert Ransford 313, James Gotto 314, Charles, Millson, Jane Bowles 318, Caradog, Thomas, Melanie Harrison 70, Roman Galaska 71, Jennie, Kendall, Jessica, Whiteman, Caroline, Lawlor, Catherine, Gray, Keith Elliott 79, Caroline Mulvaney Jones, Lucie, Hobson, Greta Van Duyvenvoorde 90, Alison Loftus 91, Katie Seward 92, Ruth, Penn, Jane Maiden 98, Rose Damant 98, Janeane Hails 101, Rebecca, Cloudsdale, Valeria Silvestre 105, Sue Glenn 106, Eleanor Dungca 107, Natalie Wheatley 108, Helen Doyle 109, Melanie, Kent, Caroline, Hamilton, Delyth, Braim, Helen Wooldridge 117, Rachel Abrahams 117, Alison Paton 119, Nicola, Lancaster, Andrew Gibbins 122, Karen Hogben 122, Phillipa, Desousa, Florin, Muscariu, Janine, Musselwhite, Alexandra McKay 132, LaiTing Tan 135, Carole Foale 138, Jacqueline Brighton 138, Kerry Flahive 140, Estelle, Nambela, Paula, Townshend, Chris, Ford, Sophie, Holder, Caroline, Palmer, James Featherstone 147, Mariam Nasseri 151, Joy Sadeghian 153, Bronwen, Williams, Carol Thomas 156, Sally Ann Rolls 156, Abigail Hynes 159, Claire Duggan 159, Sarah Jones 159, Mary, Crossey, Glynis Stansfield 163, Carolyn MacNicol 163, Joy Wilkins 164, Elva Wilhelmsen 165, Parizade Raymode 166, Hye Jeong Lee 167, Emma, Durant, Rebecca, Bishop, Noma, Ncube, Sherill, Tripoli, Rebecca, Casey, Caroline Cowley 182, Richard Miller 183, Kathryn Houghton 188, Samantha Ducker 188, Fiona Wright 189, Bridget Bird 191, Gwen Baxter 191, Janie Keggans 191, Maggie, Hughes, Emma Grieve 196, Karin Young 196, Williams 197, D., Kate Ocker 199, Frances, Hines, Kirsty, Martin, Caron, Innes, Talal Valliani 216, Helen, Fairlamb, Sarah, Thornthwaite, Anne, Eastick, Elizabeth Tanqueray 221, Jennifer Morrison 222, Becky Holbrook 222, Julie, Browning, Kirsten, Walker, Susan, Congreave, Juliette, Verheyden, Susan, Slininger, Lizzie Stafford 231, Denise O’Donnell 231, Mark Ainsworth 231, Susan Lord 118, Linda, Kent, Linda March 238, Christine Dickson 239, Diane Simpson 239, Beverley Longhurst 240, Maria Hayes 240, Ervin, Shpuza, Nikki, White, Sarah, Besley, Sallyanne Pearson 244, Alice Wright 245, Linda Jones 245, Emma Gunter 246, Hannah Dewhurst 246, Anna Fouracres 247, Liz Farrington 247, Lyn Graves 247, Suzie Marriott 248, Marina Leoni 249, David Tyrer 252, Kate Martin 252, Lola Dali kemmery 253, Victoria Lambourne 253, Marie Green 254, Dawn, Sirdefield, Kelly Amor 255, Julie Colley 258, Bal Shinder 258, Jayne Jones 260, Marisa Mills 260, Mandy, Carnahan, Natalie Taylor 265, Kerenza Boulton 265, Julie, Tregonning, Carly Brown 270, Gayle Clifford 270, Emily Archer 271, Maria, Hamilton, Janette Curtis 278, Tracey Shewan 279, Sue Walsh 280, Karen, Warner, Kimberley Netherton 283, Mcdonald Mupudzi 286, Bridget Gunson 287, Jane Gitahi 288, Denise Gocher 289, Sally, Batham, Hilary, Pateman, Senayon, Desmennu, Jill Conder 293, Darren Clement 294, Susan Gallagher 294, Jacky Orpe 256, PuiChing Chan 296, Lynn, Currie, Lynn, O’Donohoe, Metod Oblak 300, Lisa Morgan 302, Marie Quinn 303, Isobel Amey 304, Yolanda Baird 304, Donna Cotterill 305, Lourdes Cumlat 306, Louise Winter 312, Sandra Greer 312, Katie, Spurdle, Joanna, Allison, Simon, Dyer, Helen, Sweeting, Jean, Kordula, Cordell, H. J., Han, Y., Mells, G. F., Li, Y., Hirschfield, G. M., Greene, C. S., Xie, G., Juran, B. D., Zhu, D., Qian, D. C., Floyd, J. A. B., Morley, K. I., Prati, D., Lleo, A., Cusi, D., Gershwin, M. E., Anderson, C. A., Lazaridis, K. N., Invernizzi, P., Seldin, M. F., Sandford, R. N., Amos, C. I., Siminovitch, K. A., Schlicht, E. M., Lammert, C., Atkinson, E. J., Chan, L. L., De Andrade, M., Balschun, T., Mason, A. L., Myers, R. P., Zhang, J., Milkiewicz, P., Qu, J., Odin, J. A., Luketic, V. A., Bacon, B. R., Bodenheimer, H. C., Liakina, V., Vincent, C., Levy, C., Gregersen, P. K., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Barlassina, C., Battezzati, P. M., Benedetti, A., Bernuzzi, F., Bianchi, I., Bragazzi, M. C., Brunetto, M., Bruno, S., Casella, G., Coco, B., Colli, A., Colombo, M., Colombo, S., Cursaro, C., Croce, L. S., Crosignani, A., Donato, M. F., Elia, G., Fabris, L., Ferrari, C., Floreani, A., Foglieni, B., Fontana, R., Galli, A., Lazzari, R., Macaluso, F., Malinverno, F., Marra, F., Marzioni, M., Mattalia, A., Montanari, R., Morini, L., Morisco, F., Mousa Hani, S., Muratori, L., Muratori, P., Niro, G. A., Palmieri, V. O., Picciotto, A., Podda, M., Portincasa, P., Ronca, V., Rosina, F., Rossi, S., Sogno, I., Spinzi, G., Spreafico, M., Strazzabosco, M., Tarallo, S., Tarocchi, M., Tiribelli, C., Toniutto, P., Vinci, M., Zuin, M., Ch'Ng, C. L., Rahman, M., Yapp, T., Sturgess, R., Healey, C., Czajkowski, M., Gunasekera, A., Gyawali, P., Premchand, P., Kapur, K., Marley, R., Foster, G., Watson, A., Dias, A., Subhani, J., Harvey, R., Mccorry, R., Ramanaden, D., Gasem, J., Evans, R., Mathialahan, T., Shorrock, C., Lipscomb, G., Southern, P., Tibble, J., Gorard, D., Palegwala, A., Jones, S., Carbone, M., Dawwas, M., Alexander, G., Dolwani, S., Prince, M., Foxton, M., Elphick, D., Mitchison, H., Gooding, I., Karmo, M., Saksena, S., Mendall, M., Patel, M., Ede, R., Austin, A., Sayer, J., Hankey, L., Hovell, C., Fisher, N., Carter, M., Koss, K., Piotrowicz, A., Grimley, C., Neal, D., Lim, G., Levi, S., Ala, A., Broad, A., Saeed, A., Wood, G., Brown, J., Wilkinson, M., Gordon, H., Ramage, J., Ridpath, J., Ngatchu, T., Grover, B., Shaukat, S., Shidrawi, R., Abouda, G., Ali, F., Rees, I., Salam, I., Narain, M., Brown, A., Taylor-Robinson, S., Williams, S., Grellier, L., Banim, P., Das, D., Chilton, A., Heneghan, M., Curtis, H., Gess, M., Drake, I., Aldersley, M., Davies, M., Jones, R., Mcnair, A., Srirajaskanthan, R., Pitcher, M., Sen, S., Bird, G., Barnardo, A., Kitchen, P., Yoong, K., Chirag, O., Sivaramakrishnan, N., Macfaul, G., Jones, D., Shah, A., Evans, C., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Fraser, A., Mills, P., Shallcross, C., Campbell, S., Bathgate, A., Shepherd, A., Dillon, J., Rushbrook, S., Przemioslo, R., Macdonald, C., Metcalf, J., Shmueli, U., Davis, A., Naqvi, A., Lee, T., Stephen, D., Collier, J., Klass, H., Ninkovic, M., Cramp, M., Sharer, N., Aspinall, R., Goggin, P., Ghosh, D., Douds, A., Hoeroldt, B., Booth, J., Williams, E., Hussaini, H., Stableforth, W., Ayres, R., Thorburn, D., Marshall, E., Burroughs, A., Mann, S., Lombard, M., Richardson, P., Patanwala, I., Maltby, J., Brookes, M., Mathew, R., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Panter, S., Shearman, J., Bray, G., Butcher, G., Forton, D., Mclindon, J., Cowan, M., Whatley, G., Mandal, A., Gupta, H., Sanghi, P., Jain, S., Pereira, S., Prasad, G., Watts, G., Wright, M., Neuberger, J., Gordon, F., Unitt, E., Grant, A., Delahooke, T., Higham, A., Brind, A., Cox, M., Ramakrishnan, S., King, A., Collins, C., Whalley, S., Li, A., Fraser, J., Bell, A., Wong, V. S., Singhal, A., Gee, I., Ang, Y., Ransford, R., Gotto, J., Millson, C., Bowles, J., Thomas, C., Harrison, M., Galaska, R., Kendall, J., Whiteman, J., Lawlor, C., Gray, C., Elliott, K., Mulvaney-Jones, C., Hobson, L., Van Duyvenvoorde, G., Loftus, A., Seward, K., Penn, R., Maiden, J., Damant, R., Hails, J., Cloudsdale, R., Silvestre, V., Glenn, S., Dungca, E., Wheatley, N., Doyle, H., Kent, M., Hamilton, C., Braim, D., Wooldridge, H., Abrahams, R., Paton, A., Lancaster, N., Gibbins, A., Hogben, K., Desousa, P., Muscariu, F., Musselwhite, J., Mckay, A., Tan, L., Foale, C., Brighton, J., Flahive, K., Nambela, E., Townshend, P., Ford, C., Holder, S., Palmer, C., Featherstone, J., Nasseri, M., Sadeghian, J., Williams, B., Rolls, S. -A., Hynes, A., Duggan, C., Crossey, M., Stansfield, G., Macnicol, C., Wilkins, J., Wilhelmsen, E., Raymode, P., Lee, H. -J., Durant, E., Bishop, R., Ncube, N., Tripoli, S., Casey, R., Cowley, C., Miller, R., Houghton, K., Ducker, S., Wright, F., Bird, B., Baxter, G., Keggans, J., Hughes, M., Grieve, E., Young, K., Williams, D., Ocker, K., Hines, F., Martin, K., Innes, C., Valliani, T., Fairlamb, H., Thornthwaite, S., Eastick, A., Tanqueray, E., Morrison, J., Holbrook, B., Browning, J., Walker, K., Congreave, S., Verheyden, J., Slininger, S., Stafford, L., O'Donnell, D., Ainsworth, M., Lord, S., Kent, L., March, L., Dickson, C., Simpson, D., Longhurst, B., Hayes, M., Shpuza, E., White, N., Besley, S., Pearson, S., Wright, A., Jones, L., Gunter, E., Dewhurst, H., Fouracres, A., Farrington, L., Graves, L., Marriott, S., Leoni, M., Tyrer, D., Dali-Kemmery, L., Lambourne, V., Green, M., Sirdefield, D., Amor, K., Colley, J., Shinder, B., Jones, J., Mills, M., Carnahan, M., Taylor, N., Boulton, K., Tregonning, J., Brown, C., Clifford, G., Archer, E., Hamilton, M., Curtis, J., Shewan, T., Walsh, S., Warner, K., Netherton, K., Mupudzi, M., Gunson, B., Gitahi, J., Gocher, D., Batham, S., Pateman, H., Desmennu, S., Conder, J., Clement, D., Gallagher, S., Orpe, J., Chan, P., Currie, L., O'Donohoe, L., Oblak, M., Morgan, L., Quinn, M., Amey, I., Baird, Y., Cotterill, D., Cumlat, L., Winter, L., Greer, S., Spurdle, K., Allison, J., Dyer, S., Sweeting, H., Kordula, J., Cordell, Heather J, Han, Younghun, Mells, George F., Li, Yafang, Hirschfield, Gideon M., Greene, Casey S., Xie, Gang, Juran, Brian D., Zhu, Dakai, Qian, David C., Floyd, James A. B., Morley, Katherine I., Prati, Daniele, Lleo, Ana, Cusi, Daniele, Gershwin, M. Eric, Anderson, Carl A., Lazaridis, Konstantinos N., Invernizzi, Pietro, Seldin, Michael F., Sandford, Richard N., Amos, Christopher I., Siminovitch, Katherine A., Schlicht, Erik M., Lammert, Craig, Atkinson, Elizabeth J., Chan, Landon L., De Andrade, Mariza, Balschun, Tobia, Mason, Andrew L., Myers, Robert P., Zhang, Jinyi, Milkiewicz, Piotr, Qu, Jia, Odin, Joseph A., Luketic, Velimir A., Bacon, Bruce R., Bodenheimer, Henry C., Liakina, Valentina, Vincent, Catherine, Levy, Cynthia, Gregersen, Peter K., Almasio, Piero L., Alvaro, Domenico, Andreone, Pietro, Andriulli, Angelo, Barlassina, Cristina, Battezzati, Pier Maria, Benedetti, Antonio, Bernuzzi, Francesca, Bianchi, Ilaria, Bragazzi, Maria Consiglia, Brunetto, Maurizia, Bruno, Savino, Casella, Giovanni, Coco, Barbara, Colli, Agostino, Colombo, Massimo, Colombo, Silvia, Cursaro, Carmela, Crocè, Lory Saveria, Crosignani, Andrea, Donato, Maria Francesca, Elia, Gianfranco, Fabris, Luca, Ferrari, Carlo, Floreani, Annarosa, Foglieni, Barbara, Fontana, Rosanna, Galli, Andrea, Lazzari, Roberta, Macaluso, Fabio, Malinverno, Federica, Marra, Fabio, Marzioni, Marco, Mattalia, Alberto, Montanari, Renzo, Morini, Lorenzo, Morisco, Filomena, Muratori, Luigi, Muratori, Paolo, Niro, Grazia A., Palmieri, Vincenzo O., Picciotto, Antonio, Podda, Mauro, Portincasa, Piero, Ronca, Vincenzo, Rosina, Floriano, Rossi, Sonia, Sogno, Ilaria, Spinzi, Giancarlo, Spreafico, Marta, Strazzabosco, Mario, Tarallo, Sonia, Tarocchi, Mirko, Tiribelli, Claudio, Toniutto, Pierluigi, Vinci, Maria, Zuin, Massimo, Ch'Ng, Chin Lye, Rahman, Mesbah, Yapp, Tom, Sturgess, Richard, Healey, Christopher, Czajkowski, Marek, Gunasekera, Anton, Gyawali, Pranab, Premchand, Purushothaman, Kapur, Kapil, Marley, Richard, Foster, Graham, Watson, Alan, Dias, Aruna, Subhani, Javaid, Harvey, Rory, Mccorry, Roger, Ramanaden, David, Gasem, Jaber, Evans, Richard, Mathialahan, Thiriloganathan, Shorrock, Christopher, Lipscomb, George, Southern, Paul, Tibble, Jeremy, Gorard, David, Palegwala, Altaf, Jones, Susan, Carbone, Marco, Dawwas, Mohamed, Alexander, Graeme, Dolwani, Sunil, Prince, Martin, Foxton, Matthew, Elphick, David, Mitchison, Harriet, Gooding, Ian, Karmo, Mazn, Saksena, Sushma, Mendall, Mike, Patel, Minesh, Ede, Roland, Austin, Andrew, Sayer, Joanna, Hankey, Lorraine, Hovell, Christopher, Fisher, Neil, Carter, Martyn, Koss, Konrad, Piotrowicz, Andrzej, Grimley, Charle, Neal, David, Lim, Guan, Levi, Sa, Ala, Aftab, Broad, Andrea, Saeed, Athar, Wood, Gordon, Brown, Jonathan, Wilkinson, Mark, Gordon, Harriet, Ramage, John, Ridpath, Jo, Ngatchu, Theodore, Grover, Bob, Shaukat, Syed, Shidrawi, Ray, Abouda, George, Ali, Faiz, Rees, Ian, Salam, Imroz, Narain, Mark, Brown, Ashley, Taylor-Robinson, Simon, Williams, Simon, Grellier, Leonie, Banim, Paul, Das, Debasish, Chilton, Andrew, Heneghan, Michael, Curtis, Howard, Gess, Marku, Drake, Ian, Aldersley, Mark, Davies, Mervyn, Jones, Rebecca, Mcnair, Alastair, Srirajaskanthan, Raj, Pitcher, Maxton, Sen, Sambit, Bird, George, Barnardo, Adrian, Kitchen, Paul, Yoong, Kevin, Chirag, Oza, Sivaramakrishnan, Nurani, Macfaul, George, Jones, David, Shah, Amir, Evans, Chri, Saha, Subrata, Pollock, Katharine, Bramley, Peter, Mukhopadhya, Ashi, Fraser, Andrew, Mills, Peter, Shallcross, Christopher, Campbell, Stewart, Bathgate, Andrew, Shepherd, Alan, Dillon, John, Rushbrook, Simon, Przemioslo, Robert, Macdonald, Christopher, Metcalf, Jane, Shmueli, Udi, Davis, Andrew, Naqvi, Asifabba, Lee, Tom, Stephen, Dyder, Collier, Jane, Klass, Howard, Ninkovic, Mary, Cramp, Matthew, Sharer, Nichola, Aspinall, Richard, Goggin, Patrick, Ghosh, Deb, Douds, Andrew, Hoeroldt, Barbara, Booth, Jonathan, Williams, Earl, Hussaini, Hyder, Stableforth, William, Ayres, Reuben, Thorburn, Dougla, Marshall, Eileen, Burroughs, Andrew, Mann, Steven, Lombard, Martin, Richardson, Paul, Patanwala, Imran, Maltby, Julia, Brookes, Matthew, Mathew, Ray, Vyas, Samir, Singhal, Saket, Gleeson, Dermot, Misra, Sharat, Butterworth, Jeff, George, Keith, Harding, Tim, Douglass, Andrew, Panter, Simon, Shearman, Jeremy, Bray, Gary, Butcher, Graham, Forton, Daniel, Mclindon, John, Cowan, Matthew, Whatley, Gregory, Mandal, Aditya, Gupta, Hemant, Sanghi, Pradeep, Jain, Sanjiv, Pereira, Steve, Prasad, Geeta, Watts, Gill, Wright, Mark, Neuberger, Jame, Gordon, Fiona, Unitt, Esther, Grant, Allister, Delahooke, Toby, Higham, Andrew, Brind, Alison, Cox, Mark, Ramakrishnan, Subramaniam, King, Alistair, Collins, Carole, Whalley, Simon, Li, Andy, Fraser, Jocelyn, Bell, Andrew, Wong, Voi Shim, Singhal, Amit, Gee, Ian, Ang, Yeng, Ransford, Rupert, Gotto, Jame, Millson, Charle, Bowles, Jane, Thomas, Caradog, Harrison, Melanie, Galaska, Roman, Kendall, Jennie, Whiteman, Jessica, Lawlor, Caroline, Gray, Catherine, Elliott, Keith, Mulvaney-Jones, Caroline, Hobson, Lucie, Van Duyvenvoorde, Greta, Loftus, Alison, Seward, Katie, Penn, Ruth, Maiden, Jane, Damant, Rose, Hails, Janeane, Cloudsdale, Rebecca, Silvestre, Valeria, Glenn, Sue, Dungca, Eleanor, Wheatley, Natalie, Doyle, Helen, Kent, Melanie, Hamilton, Caroline, Braim, Delyth, Wooldridge, Helen, Abrahams, Rachel, Paton, Alison, Lancaster, Nicola, Gibbins, Andrew, Hogben, Karen, Desousa, Phillipa, Muscariu, Florin, Musselwhite, Janine, Mckay, Alexandra, Tan, Laiting, Foale, Carole, Brighton, Jacqueline, Flahive, Kerry, Nambela, Estelle, Townshend, Paula, Ford, Chri, Holder, Sophie, Palmer, Caroline, Featherstone, Jame, Nasseri, Mariam, Sadeghian, Joy, Williams, Bronwen, Thomas, Carol, Rolls, Sally-Ann, Hynes, Abigail, Duggan, Claire, Jones, Sarah, Crossey, Mary, Stansfield, Glyni, Macnicol, Carolyn, Wilkins, Joy, Wilhelmsen, Elva, Raymode, Parizade, Lee, Hye-Jeong, Durant, Emma, Bishop, Rebecca, Ncube, Noma, Tripoli, Sherill, Casey, Rebecca, Cowley, Caroline, Miller, Richard, Houghton, Kathryn, Ducker, Samantha, Wright, Fiona, Bird, Bridget, Baxter, Gwen, Keggans, Janie, Hughes, Maggie, Grieve, Emma, Young, Karin, Ocker, Kate, Hines, France, Martin, Kirsty, Innes, Caron, Valliani, Talal, Fairlamb, Helen, Thornthwaite, Sarah, Eastick, Anne, Tanqueray, Elizabeth, Morrison, Jennifer, Holbrook, Becky, Browning, Julie, Walker, Kirsten, Congreave, Susan, Verheyden, Juliette, Slininger, Susan, Stafford, Lizzie, O'Donnell, Denise, Ainsworth, Mark, Lord, Susan, Kent, Linda, March, Linda, Dickson, Christine, Simpson, Diane, Longhurst, Beverley, Hayes, Maria, Shpuza, Ervin, White, Nikki, Besley, Sarah, Pearson, Sallyanne, Wright, Alice, Jones, Linda, Gunter, Emma, Dewhurst, Hannah, Fouracres, Anna, Farrington, Liz, Graves, Lyn, Marriott, Suzie, Leoni, Marina, Tyrer, David, Martin, Kate, Dali-Kemmery, Lola, Lambourne, Victoria, Green, Marie, Sirdefield, Dawn, Amor, Kelly, Colley, Julie, Shinder, Bal, Jones, Jayne, Mills, Marisa, Carnahan, Mandy, Taylor, Natalie, Boulton, Kerenza, Tregonning, Julie, Brown, Carly, Clifford, Gayle, Archer, Emily, Hamilton, Maria, Curtis, Janette, Shewan, Tracey, Walsh, Sue, Warner, Karen, Netherton, Kimberley, Mupudzi, Mcdonald, Gunson, Bridget, Gitahi, Jane, Gocher, Denise, Batham, Sally, Pateman, Hilary, Desmennu, Senayon, Conder, Jill, Clement, Darren, Gallagher, Susan, Orpe, Jacky, Chan, Puiching, Currie, Lynn, O'Donohoe, Lynn, Oblak, Metod, Morgan, Lisa, Quinn, Marie, Amey, Isobel, Baird, Yolanda, Cotterill, Donna, Cumlat, Lourde, Winter, Louise, Greer, Sandra, Spurdle, Katie, Allison, Joanna, Dyer, Simon, Sweeting, Helen, Kordula, Jean, Heather J., Cordell, Younghun, Han, George F., Mell, Yafang, Li, Gideon M., Hirschfield, Casey S., Greene, Gang, Xie, Brian D., Juran, Dakai, Zhu, David C., Qian, James A. B., Floyd, Katherine I., Morley, Daniele, Prati, Ana, Lleo, Daniele, Cusi, Canadian US PBC, Consortium, Italian PBC Genetics Study, Group, UK PBC, Consortium, M., Eric Gershwin, Carl A., Anderson, Konstantinos N., Lazaridi, Pietro, Invernizzi, Michael F., Seldin, Richard N., Sandford, Christopher I., Amo, Katherine A., Siminovitch, Cordell H.J., Han Y., Mells G.F., Li Y., Hirschfield G.M., Greene C.S., Xie G., Juran B.D., Zhu D., Qian D.C., Floyd J.A.B., Morley K.I., Prati D., Lleo A., Cusi D., Gershwin M.E., Anderson C.A., Lazaridis K.N., Invernizzi P., Seldin M.F., Sandford R.N., Amos C.I., Siminovitch K.A., Schlicht E.M., Lammert C., Atkinson E.J., Chan L.L., De Andrade M., Balschun T., Mason A.L., Myers R.P., Zhang J., Milkiewicz P., Qu J., Odin J.A., Luketic V.A., Bacon B.R., Bodenheimer H.C., Liakina V., Vincent C., Levy C., Gregersen P.K., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Barlassina C., Battezzati P.M., Benedetti A., Bernuzzi F., Bianchi I., Bragazzi M.C., Brunetto M., Bruno S., Casella G., Coco B., Colli A., Colombo M., Colombo S., Cursaro C., Croce L.S., Crosignani A., Donato M.F., Elia G., Fabris L., Ferrari C., Floreani A., Foglieni B., Fontana R., Galli A., Lazzari R., Macaluso F., Malinverno F., Marra F., Marzioni M., Mattalia A., Montanari R., Morini L., Morisco F., Mousa Hani S., Muratori L., Muratori P., Niro G.A., Palmieri V.O., Picciotto A., Podda M., Portincasa P., Ronca V., Rosina F., Rossi S., Sogno I., Spinzi G., Spreafico M., Strazzabosco M., Tarallo S., Tarocchi M., Tiribelli C., Toniutto P., Vinci M., Zuin M., Ch'Ng C.L., Rahman M., Yapp T., Sturgess R., Healey C., Czajkowski M., Gunasekera A., Gyawali P., Premchand P., Kapur K., Marley R., Foster G., Watson A., Dias A., Subhani J., Harvey R., McCorry R., Ramanaden D., Gasem J., Evans R., Mathialahan T., Shorrock C., Lipscomb G., Southern P., Tibble J., Gorard D., Palegwala A., Jones S., Carbone M., Dawwas M., Alexander G., Dolwani S., Prince M., Foxton M., Elphick D., Mitchison H., Gooding I., Karmo M., Saksena S., Mendall M., Patel M., Ede R., Austin A., Sayer J., Hankey L., Hovell C., Fisher N., Carter M., Koss K., Piotrowicz A., Grimley C., Neal D., Lim G., Levi S., Ala A., Broad A., Saeed A., Wood G., Brown J., Wilkinson M., Gordon H., Ramage J., Ridpath J., Ngatchu T., Grover B., Shaukat S., Shidrawi R., Abouda G., Ali F., Rees I., Salam I., Narain M., Brown A., Taylor-Robinson S., Williams S., Grellier L., Banim P., Das D., Chilton A., Heneghan M., Curtis H., Gess M., Drake I., Aldersley M., Davies M., Jones R., McNair A., Srirajaskanthan R., Pitcher M., Sen S., Bird G., Barnardo A., Kitchen P., Yoong K., Chirag O., Sivaramakrishnan N., MacFaul G., Jones D., Shah A., Evans C., Saha S., Pollock K., Bramley P., Mukhopadhya A., Fraser A., Mills P., Shallcross C., Campbell S., Bathgate A., Shepherd A., Dillon J., Rushbrook S., Przemioslo R., Macdonald C., Metcalf J., Shmueli U., Davis A., Naqvi A., Lee T., Stephen D., Collier J., Klass H., Ninkovic M., Cramp M., Sharer N., Aspinall R., Goggin P., Ghosh D., Douds A., Hoeroldt B., Booth J., Williams E., Hussaini H., Stableforth W., Ayres R., Thorburn D., Marshall E., Burroughs A., Mann S., Lombard M., Richardson P., Patanwala I., Maltby J., Brookes M., Mathew R., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Panter S., Shearman J., Bray G., Butcher G., Forton D., McLindon J., Cowan M., Whatley G., Mandal A., Gupta H., Sanghi P., Jain S., Pereira S., Prasad G., Watts G., Wright M., Neuberger J., Gordon F., Unitt E., Grant A., Delahooke T., Higham A., Brind A., Cox M., Ramakrishnan S., King A., Collins C., Whalley S., Li A., Fraser J., Bell A., Wong V.S., Singhal A., Gee I., Ang Y., Ransford R., Gotto J., Millson C., Bowles J., Thomas C., Harrison M., Galaska R., Kendall J., Whiteman J., Lawlor C., Gray C., Elliott K., Mulvaney-Jones C., Hobson L., Van Duyvenvoorde G., Loftus A., Seward K., Penn R., Maiden J., Damant R., Hails J., Cloudsdale R., Silvestre V., Glenn S., Dungca E., Wheatley N., Doyle H., Kent M., Hamilton C., Braim D., Wooldridge H., Abrahams R., Paton A., Lancaster N., Gibbins A., Hogben K., Desousa P., Muscariu F., Musselwhite J., McKay A., Tan L., Foale C., Brighton J., Flahive K., Nambela E., Townshend P., Ford C., Holder S., Palmer C., Featherstone J., Nasseri M., Sadeghian J., Williams B., Rolls S.-A., Hynes A., Duggan C., Crossey M., Stansfield G., MacNicol C., Wilkins J., Wilhelmsen E., Raymode P., Lee H.-J., Durant E., Bishop R., Ncube N., Tripoli S., Casey R., Cowley C., Miller R., Houghton K., Ducker S., Wright F., Bird B., Baxter G., Keggans J., Hughes M., Grieve E., Young K., Williams D., Ocker K., Hines F., Martin K., Innes C., Valliani T., Fairlamb H., Thornthwaite S., Eastick A., Tanqueray E., Morrison J., Holbrook B., Browning J., Walker K., Congreave S., Verheyden J., Slininger S., Stafford L., O'Donnell D., Ainsworth M., Lord S., Kent L., March L., Dickson C., Simpson D., Longhurst B., Hayes M., Shpuza E., White N., Besley S., Pearson S., Wright A., Jones L., Gunter E., Dewhurst H., Fouracres A., Farrington L., Graves L., Marriott S., Leoni M., Tyrer D., Dali-Kemmery L., Lambourne V., Green M., Sirdefield D., Amor K., Colley J., Shinder B., Jones J., Mills M., Carnahan M., Taylor N., Boulton K., Tregonning J., Brown C., Clifford G., Archer E., Hamilton M., Curtis J., Shewan T., Walsh S., Warner K., Netherton K., Mupudzi M., Gunson B., Gitahi J., Gocher D., Batham S., Pateman H., Desmennu S., Conder J., Clement D., Gallagher S., Orpe J., Chan P., Currie L., O'Donohoe L., Oblak M., Morgan L., Quinn M., Amey I., Baird Y., Cotterill D., Cumlat L., Winter L., Greer S., Spurdle K., Allison J., Dyer S., Sweeting H., Kordula J., Cordell, H, Han, Y, Mells, G, Li, Y, Hirschfield, G, Greene, C, Xie, G, Juran, B, Zhu, D, Qian, D, Floyd, J, Morley, K, Prati, D, Lleo, A, Cusi, D, Gershwin, M, Anderson, C, Lazaridis, K, Invernizzi, P, Seldin, M, Sandford, R, Amos, C, Siminovitch, K, Schlicht, E, Lammert, C, Atkinson, E, Chan, L, De Andrade, M, Balschun, T, Mason, A, Myers, R, Zhang, J, Milkiewicz, P, Qu, J, Odin, J, Luketic, V, Bacon, B, Bodenheimer, H, Liakina, V, Vincent, C, Levy, C, Gregersen, P, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Battezzati, P, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, M, Brunetto, M, Bruno, S, Casella, G, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Crocè, L, Crosignani, A, Donato, M, Elia, G, Fabris, L, Ferrari, C, Floreani, A, Foglieni, B, Fontana, R, Galli, A, Lazzari, R, Macaluso, F, Malinverno, F, Marra, F, Marzioni, M, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Mousa Hani, S, Muratori, L, Muratori, P, Niro, G, Palmieri, V, Picciotto, A, Podda, M, Portincasa, P, Ronca, V, Rosina, F, Rossi, S, Sogno, I, Spinzi, G, Spreafico, M, Strazzabosco, M, Tarallo, S, Tarocchi, M, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, Ch'Ng, C, Rahman, M, Yapp, T, Sturgess, R, Healey, C, Czajkowski, M, Gunasekera, A, Gyawali, P, Premchand, P, Kapur, K, Marley, R, Foster, G, Watson, A, Dias, A, Subhani, J, Harvey, R, Mccorry, R, Ramanaden, D, Gasem, J, Evans, R, Mathialahan, T, Shorrock, C, Lipscomb, G, Southern, P, Tibble, J, Gorard, D, Palegwala, A, Jones, S, Carbone, M, Dawwas, M, Alexander, G, Dolwani, S, Prince, M, Foxton, M, Elphick, D, Mitchison, H, Gooding, I, Karmo, M, Saksena, S, Mendall, M, Patel, M, Ede, R, Austin, A, Sayer, J, Hankey, L, Hovell, C, Fisher, N, Carter, M, Koss, K, Piotrowicz, A, Grimley, C, Neal, D, Lim, G, Levi, S, Ala, A, Broad, A, Saeed, A, Wood, G, Brown, J, Wilkinson, M, Gordon, H, Ramage, J, Ridpath, J, Ngatchu, T, Grover, B, Shaukat, S, Shidrawi, R, Abouda, G, Ali, F, Rees, I, Salam, I, Narain, M, Brown, A, Taylor Robinson, S, Williams, S, Grellier, L, Banim, P, Das, D, Chilton, A, Heneghan, M, Curtis, H, Gess, M, Drake, I, Aldersley, M, Davies, M, Jones, R, Mcnair, A, Srirajaskanthan, R, Pitcher, M, Sen, S, Bird, G, Barnardo, A, Kitchen, P, Yoong, K, Chirag, O, Sivaramakrishnan, N, Macfaul, G, Jones, D, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Fraser, A, Mills, P, Shallcross, C, Campbell, S, Bathgate, A, Shepherd, A, Dillon, J, Rushbrook, S, Przemioslo, R, Macdonald, C, Metcalf, J, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Stephen, D, Collier, J, Klass, H, Ninkovic, M, Cramp, M, Sharer, N, Aspinall, R, Goggin, P, Ghosh, D, Douds, A, Hoeroldt, B, Booth, J, Williams, E, Hussaini, H, Stableforth, W, Ayres, R, Thorburn, D, Marshall, E, Burroughs, A, Mann, S, Lombard, M, Richardson, P, Patanwala, I, Maltby, J, Brookes, M, Mathew, R, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Panter, S, Shearman, J, Bray, G, Butcher, G, Forton, D, Mclindon, J, Cowan, M, Whatley, G, Mandal, A, Gupta, H, Sanghi, P, Jain, S, Pereira, S, Prasad, G, Watts, G, Wright, M, Neuberger, J, Gordon, F, Unitt, E, Grant, A, Delahooke, T, Higham, A, Brind, A, Cox, M, Ramakrishnan, S, King, A, Collins, C, Whalley, S, Li, A, Fraser, J, Bell, A, Wong, V, Singhal, A, Gee, I, Ang, Y, Ransford, R, Gotto, J, Millson, C, Bowles, J, Thomas, C, Harrison, M, Galaska, R, Kendall, J, Whiteman, J, Lawlor, C, Gray, C, Elliott, K, Mulvaney Jones, C, Hobson, L, Van Duyvenvoorde, G, Loftus, A, Seward, K, Penn, R, Maiden, J, Damant, R, Hails, J, Cloudsdale, R, Silvestre, V, Glenn, S, Dungca, E, Wheatley, N, Doyle, H, Kent, M, Hamilton, C, Braim, D, Wooldridge, H, Abrahams, R, Paton, A, Lancaster, N, Gibbins, A, Hogben, K, Desousa, P, Muscariu, F, Musselwhite, J, Mckay, A, Tan, L, Foale, C, Brighton, J, Flahive, K, Nambela, E, Townshend, P, Ford, C, Holder, S, Palmer, C, Featherstone, J, Nasseri, M, Sadeghian, J, Williams, B, Rolls, S, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, Durant, E, Bishop, R, Ncube, N, Tripoli, S, Casey, R, Cowley, C, Miller, R, Houghton, K, Ducker, S, Wright, F, Bird, B, Baxter, G, Keggans, J, Hughes, M, Grieve, E, Young, K, Williams, D, Ocker, K, Hines, F, Martin, K, Innes, C, Valliani, T, Fairlamb, H, Thornthwaite, S, Eastick, A, Tanqueray, E, Morrison, J, Holbrook, B, Browning, J, Walker, K, Congreave, S, Verheyden, J, Slininger, S, Stafford, L, O'Donnell, D, Ainsworth, M, Lord, S, Kent, L, March, L, Dickson, C, Simpson, D, Longhurst, B, Hayes, M, Shpuza, E, White, N, Besley, S, Pearson, S, Wright, A, Jones, L, Gunter, E, Dewhurst, H, Fouracres, A, Farrington, L, Graves, L, Marriott, S, Leoni, M, Tyrer, D, Dali Kemmery, L, Lambourne, V, Green, M, Sirdefield, D, Amor, K, Colley, J, Shinder, B, Jones, J, Mills, M, Carnahan, M, Taylor, N, Boulton, K, Tregonning, J, Brown, C, Clifford, G, Archer, E, Hamilton, M, Curtis, J, Shewan, T, Walsh, S, Warner, K, Netherton, K, Mupudzi, M, Gunson, B, Gitahi, J, Gocher, D, Batham, S, Pateman, H, Desmennu, S, Conder, J, Clement, D, Gallagher, S, Orpe, J, Chan, P, Currie, L, O'Donohoe, L, Oblak, M, Morgan, L, Quinn, M, Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, and Kordula, J

Subjects
Liver Cirrhosis, Genetics and Molecular Biology (all), pathogenesi, risk assessment EMTREE medical terms: Article, genetic association, genotype, EMTREE drug terms: chemokine receptor CCR6, genetic risk, Biochemistry, meta-analysi, primary biliary cirrhosi, chemokine receptor CCR6 [EMTREE drug terms], single nucleotide polymorphism, genetic variability, Article [risk assessment EMTREE medical terms], Liver Cirrhosis, Biliary, pathogenesis, Biliary, Chemistry (all), STAT protein GEOBASE Subject Index: disease treatment, cohort analysis, genome wide meta analysis PBC, signal transduction, gene locus, cohort analysi, CBP, Article, Physics and Astronomy (all), macrophage inflammatory protein 3alpha, Humans, controlled study, human, interleukin 27, genome, Biochemistry, Genetics and Molecular Biology (all), meta analysi, interleukin 12p40, interleukin 12, Janus kinase, meta-analysis, pathogen, genetic predisposition, major clinical study, meta analysis, primary biliary cirrhosis, disease treatment [STAT protein GEOBASE Subject Index], Genome-Wide Association Study, gene locu
Abstract

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined, Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Published
2015
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147. Development and validation of a novel Barrett's oesophagus patient reported outcome measure (B-PROM).

Author

Ratcliffe E, Britton J, Baines S, Prasad N, Keld R, Murgatroyd M, Montenegro M, Viloria E, McLaughlin J, Hamdy S, and Ang Y

Abstract

Background: Patients with Barrett's oesophagus (BO) carry significant cancer worry, burden of symptoms, and lack disease-specific knowledge. Currently there is no validated BO patient reported outcome measure (PROM) to measure these factors for use in clinical practice and research, hence the aim of this study was to devise a novel, validated BO-specific tool, B-PROM., Methods: Literature review, quantitative and qualitative research informed the initial item generation. The item bank was refined through a modified Delphi process between May and August 2021. The PROM was then tested through cognitive interviews and validated via multicentre testing between September 2021 and February 2023 with the aim to create a succinct tool which addresses the key important factors to BO patients and has strong psychometric properties., Findings: B-PROM covers key themes of disease-specific knowledge, trust in clinicians, burden of symptoms, cancer worry and burden of surveillance. Validation results from 387 participants (response rate 40.8%) showed 93.3% of participants completed >95% of B-PROM. All individual items scored a completion rate of >95%. Mean completion time was 5 mins 34s for a sample group. Nineteen items showed a ceiling effect, 3 items showed a floor effect. Internal consistency overall demonstrated a Cronbach Alpha of 0.846, while predetermined subsections showed Cronbach alphas of 0.335, 0.718, 0.736, and 0.896. Inter-item analysis found 2 pairs of items with strong correlation, with only 6 items correlating weakly. Item-total correlation showed 19 items correlated well. Exploratory Factor analysis (EFA) with principal component analysis produced 5 components with Eigenvalues >1 of which 4/5 had satisfactory Cronbach alphas. Test-retest reliability showed no significant differences across single and average measures (p ≤ 0.001)., Interpretation: B-PROM is the first BO-specific PROM to be systematically evaluated. Validation findings show strong internal consistency, short completion time, low missingness and excellent test-retest reliability., Funding: Medtronic Limited ISR-2016-1077., Competing Interests: YA has received funding from cancer research UK and Medtronic Ltd. ER has received research funding from Medtronic UK and speaker honoraria from Janssen and Takeda. SH has NIHR funding for other research studies, is on the board of ESSD and holds shares in the company Phagenesis Ltd., (© 2024 Published by Elsevier Ltd.)

Published
2024
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148. Barrett's oesophagus with indefinite for dysplasia shows high rates of prevalent and incident neoplasia in a UK multicentre cohort.

Author

Kopczynska M, Ratcliffe E, Yalamanchili H, Thompson A, Nimri A, Britton J, and Ang Y

Subjects
Humans, Cohort Studies, Prospective Studies, Hyperplasia, United Kingdom epidemiology, Barrett Esophagus diagnosis, Barrett Esophagus epidemiology, Barrett Esophagus pathology, Adenocarcinoma pathology
Abstract

Aims: Barrett's oesophagus with indefinite for dysplasia (IDD) carries a risk of prevalent and incident dysplasia and oesophageal adenocarcinoma. This study seeks to determine the risk of neoplasia in a multicentre prospective IDD cohort, along with determining adherence to British Society of Gastroenterology (BSG) guidelines for management and histology reporting., Methods: This was a cohort study using prospectively collected data from pathology databases from two centres in the North West of England (UK). Cases with IDD were identified over a 10-year period. Data were obtained on patient demographics, Barrett's endoscopy findings and histology, outcomes and histological reporting., Results: 102 biopsies with IDD diagnosis in 88 patients were identified. Endoscopy was repeated in 78/88 (88%) patients. 12/78 progressed to low-grade dysplasia (15% or 2.6 per 100 person years), 6/78 (7.7%, 1.3 per 100 person years) progressed to high-grade dysplasia and 6/78 (7.7%, 1.3 per 100 person years) progressed to oesophageal adenocarcinoma. The overall incidence rate for progression to any type of dysplasia was 5.1 per 100 person years. Cox regression analysis identified longer Barrett's segment, multifocal and persistent IDD as predictors of progression to dysplasia. Histology reporting did not meet 100% adherence to the BSG histology reporting minimum dataset prior to or after the introduction of the guidelines., Conclusions: IDD carries significant risk of progression to dysplasia or neoplasia. Therefore, careful diagnosis and management aided by clear histological reporting of these cases is required to diagnose prevalent and incident neoplasia., Competing Interests: Competing interests: YA and ER receive research funding from Medtronic for other studies., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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149. Dedicated service for Barrett's oesophagus surveillance endoscopy yields higher dysplasia detection and guideline adherence in a non-tertiary setting in the UK: a 5-year comparative cohort study.

Author

Ratcliffe E, Britton J, Yalamanchili H, Rostami I, Nadir SMH, Korani M, Eruchie I, Wazirdin MA, Prasad N, Hamdy S, McLaughlin J, and Ang Y

Abstract

Objective: Barrett's oesophagus (BO) endoscopic surveillance is performed to varying quality, dedicated services may offer improved outcomes. This study compares a dedicated BO service to standard care, specifically dysplasia detection rate (DDR), guideline adherence and use of advanced imaging modalities in a non-tertiary setting., Design/method: 5-year retrospective comparative cohort study comparing a dedicated BO endoscopy service with surveillance performed on non-dedicated slots at a non-tertiary centre in the UK. All adult patients undergoing BO surveillance between 1 March 2016 and 1 March 2021 were reviewed and those who underwent endoscopy on a dedicated BO service run by endoscopists with training in BO was compared with patients receiving their BO surveillance on any other endoscopy list. Endoscopy reports, histology results and clinic letters were reviewed for DDR and British society of gastroenterology guideline adherence., Results: 921 BO procedures were included (678 patients). 574 (62%) endoscopies were on a dedicated BO list vs 348 (38%) on non-dedicated.DDR was significantly higher in the dedicated cohort 6.3% (36/568) vs 2.7% (9/337) (p=0.014). Significance was sustained when cases with indefinite for dysplasia were excluded: 4.9% 27/533 vs 0.9% 3/329 (p=0.002). Guideline adherence was significantly better on the dedicated endoscopy lists.Factors associated with dysplasia detection in regression analysis included visible lesion documentation (p=0.036), use of targeted biopsies (p=<0.001), number of biopsies obtained (p≤0.001)., Conclusions: A dedicated Barrett's service showed higher DDR and guideline adherence than standard care and may be beneficial pending randomised trial data., Competing Interests: Competing interests: ER and YA have research funding from Medtronic, YA has research funding from Cancer Research UK. ER has received honoraria for a podcast recording with Janssen and for a focus group with Takeda. SH is the director and chief scientific officer for Phagenesis and holds founder shares, he holds a patent for Anisys Go and Lyft devices and received honoraria for ESSD meeting Brussels and Chinese Dysphagia research forum., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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150. Quality of life measures in dysplastic Barrett's oesophagus are comparable to patients with non-dysplastic Barrett's oesophagus and do not improve after endoscopic therapy.

Author

Ratcliffe E, Britton J, Heal C, Keld R, Murgatroyd M, Willert R, McLaughlin J, Hamdy S, and Ang Y

Subjects
Humans, Quality of Life, Endoscopy, Barrett Esophagus pathology, Esophageal Neoplasms pathology, Adenocarcinoma pathology, Gastroesophageal Reflux
Abstract

Objective: Barrett's oesophagus (BO) is a precursor lesion, via dysplastic phases, to oesophageal adenocarcinoma. Although overall risk from BO is low, it has been shown to adversely affect health-related quality of life (HRQOL). The aim was to compare dysplastic BO patients' HRQOL pre-endoscopic therapy (pre-ET) and post-ET. The pre-ET BO group was also compared with other cohorts: non-dysplastic BO (NDBO), those with colonic polyps, gastro-oesophageal reflux disease (GORD) and healthy volunteers., Design: Participants in the pre-ET cohort were recruited prior to their endotherapy and HRQOL questionnaires provided pre-ET and post-ET. Wilcoxon rank test was used to compare the pre-ET and post-ET findings. The Pre-ET group was compared to the other cohorts' HRQOL results using multiple linear regression analysis., Results: Pre-ET group of 69 participants returned the questionnaires prior to and 42 post-ET. Both the pre-ET and post-ET group showed similar levels of cancer worry, despite the treatment. No statistical significance was found for symptoms scores, anxiety and depression or general health measures with the Short Form-36 (SF-36) Score. Education for the BO patients was overall lacking with many of the pre-ET group still reporting unanswered questions about their disease.The Pre-ET group was compared with NDBO group (N=379), GORD (N=132), colonic polyp patients (N=152) and healthy volunteers (N=48). Cancer worry was similar between the NDBO group and the Pre-ET group, despite their lower risk of progression. GORD patients had worse symptom scores from a reflux and heartburn perspective. Only the healthy group has significantly better scores in the SF-36 and improved hospital anxiety and depression scores., Conclusion: These findings suggest that there is a need to improve HRQOL for patients with BO. This should include improved education and devising-specific patient-reported outcome measures for BO to capture relevant areas of HRQOL in future studies., Competing Interests: Competing interests: ER and YA have research funding from Medtronic, YA has research funding from Cancer Research UK. ER has received honoraria for a podcast recording with Janssen and for a focus group with Takeda. SH is the director and chief scientific officer for Phagenesis and holds founder shares, he holds a patent for Anisys Go and Lyft device, and received honoraria for ESSD meeting Brussels and Chinese Dysphagia research forum., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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