Author: "Fouad Yousif" - Searchworks@Jio Institute Digital Library Search Results

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38 results on '"Fouad Yousif"'

1. Sex differences in oncogenic mutational processes

Author: Constance H. Li, Stephenie D. Prokopec, Ren X. Sun, Fouad Yousif, Nathaniel Schmitz, PCAWG Tumour Subtypes and Clinical Translation, Paul C. Boutros, and PCAWG Consortium
Subjects: Science
Abstract: There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.
Published: 2020
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2. Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations

Author: René Böttcher, Charlotte F. Kweldam, Julie Livingstone, Emilie Lalonde, Takafumi N. Yamaguchi, Vincent Huang, Fouad Yousif, Michael Fraser, Robert G. Bristow, Theodorus van der Kwast, Paul C. Boutros, Guido Jenster, and Geert J. L. H. van Leenders
Subjects: Cribriform, Intraductal carcinoma, Prostate cancer, Copy number alteration, Aggressive disease, Genomic instability, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Invasive cribriform and intraductal carcinoma (CR/IDC) is associated with adverse outcome of prostate cancer patients. The aim of this study was to determine the molecular aberrations associated with CR/IDC in primary prostate cancer, focusing on genomic instability and somatic copy number alterations (CNA). Methods Whole-slide images of The Cancer Genome Atlas Project (TCGA, N = 260) and the Canadian Prostate Cancer Genome Network (CPC-GENE, N = 199) radical prostatectomy datasets were reviewed for Gleason score (GS) and presence of CR/IDC. Genomic instability was assessed by calculating the percentage of genome altered (PGA). Somatic copy number alterations (CNA) were determined using Fisher-Boschloo tests and logistic regression. Primary analysis were performed on TCGA (N = 260) as discovery and CPC-GENE (N = 199) as validation set. Results CR/IDC growth was present in 80/260 (31%) TCGA and 76/199 (38%) CPC-GENE cases. Patients with CR/IDC and ≥ GS 7 had significantly higher PGA than men without this pattern in both TCGA (2.2 fold; p = 0.0003) and CPC-GENE (1.7 fold; p = 0.004) cohorts. CR/IDC growth was associated with deletions of 8p, 16q, 10q23, 13q22, 17p13, 21q22, and amplification of 8q24. CNAs comprised a total of 1299 gene deletions and 369 amplifications in the TCGA dataset, of which 474 and 328 events were independently validated, respectively. Several of the affected genes were known to be associated with aggressive prostate cancer such as loss of PTEN, CDH1, BCAR1 and gain of MYC. Point mutations in TP53, SPOP and FOXA1were also associated with CR/IDC, but occurred less frequently than CNAs. Conclusions CR/IDC growth is associated with increased genomic instability clustering to genetic regions involved in aggressive prostate cancer. Therefore, CR/IDC is a pathologic substrate for progressive molecular tumour derangement.
Published: 2018
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3. Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories

Author: Renea A. Taylor, Michael Fraser, Julie Livingstone, Shadrielle Melijah G. Espiritu, Heather Thorne, Vincent Huang, Winnie Lo, Yu-Jia Shiah, Takafumi N. Yamaguchi, Ania Sliwinski, Sheri Horsburgh, Alice Meng, Lawrence E. Heisler, Nancy Yu, Fouad Yousif, Melissa Papargiris, Mitchell G. Lawrence, Lee Timms, Declan G. Murphy, Mark Frydenberg, Julia F. Hopkins, Damien Bolton, David Clouston, John D. McPherson, Theodorus van der Kwast, Paul C. Boutros, Gail P. Risbridger, and Robert G. Bristow
Subjects: Science
Abstract: Men that carrierBRCA2germline mutations are at risk of developing prostate cancer. Here, the authors analyse the genomes of prostate cancer from these individuals and demonstrate increased genomic instability in comparison to sporadic prostate cancer.
Published: 2017
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4. Integrated dataset of screening hits against multiple neglected disease pathogens.

Author: Solomon Nwaka, Dominique Besson, Bernadette Ramirez, Louis Maes, An Matheeussen, Quentin Bickle, Nuha R Mansour, Fouad Yousif, Simon Townson, Suzanne Gokool, Fidelis Cho-Ngwa, Moses Samje, Shailja Misra-Bhattacharya, P K Murthy, Foluke Fakorede, Jean-Marc Paris, Clive Yeates, Robert Ridley, Wesley C Van Voorhis, and Timothy Geary
Subjects: Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract: New chemical entities are desperately needed that overcome the limitations of existing drugs for neglected diseases. Screening a diverse library of 10,000 drug-like compounds against 7 neglected disease pathogens resulted in an integrated dataset of 744 hits. We discuss the prioritization of these hits for each pathogen and the strong correlation observed between compounds active against more than two pathogens and mammalian cell toxicity. Our work suggests that the efficiency of early drug discovery for neglected diseases can be enhanced through a collaborative, multi-pathogen approach.
Published: 2011
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5. Genetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways.

Author: Mohan Babu, J Javier Díaz-Mejía, James Vlasblom, Alla Gagarinova, Sadhna Phanse, Chris Graham, Fouad Yousif, Huiming Ding, Xuejian Xiong, Anaies Nazarians-Armavil, Md Alamgir, Mehrab Ali, Oxana Pogoutse, Asaf Pe'er, Roland Arnold, Magali Michaut, John Parkinson, Ashkan Golshani, Chris Whitfield, Shoshana J Wodak, Gabriel Moreno-Hagelsieb, Jack F Greenblatt, and Andrew Emili
Subjects: Genetics, QH426-470
Abstract: As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among > 235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target.
Published: 2011
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6. The Effect of Applying Neural Network Information Systems in Achieving Parallel Processing of Decisions and Streamlining Smart Solutions for Human Resources: An Applied study of a Sample of Educational Leaders at Al-Mustansiriyah University

Author: Abdul-Rahman, Fouad Yousif, primary
Published: 2023
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7. Entrepreneurship Creativity in Light of the Digitization of Mental Abilities According to the Hermann Scale': An Applied Study in the Presidency of Al-Mustansiriya University

Author: Dr. Fouad Yousif Abdulrahman, Dr. Sumaya Abbas Majeed Al-Rubaye, and Dr. Sahar Ahmed Kurji
Subjects: General Medicine
Abstract: This study was based on the idea that the study of mental abilities and the possibility of digitizing them and determining their trends according to the Hermann scale, in which he identified specific functions of the four brain departments (objective - executive - emotional - creative) an effective and important role in the advancement of the components of entrepreneurial creativity in the research organization. Where the researchers adopted the descriptive, analytical and statistical approach in dealing with variables based on measures consistent with the objectives and nature of the environment under study. He expressed the problem of the study with a set of questions of a theoretical and practical nature, which were formulated in the hypothetical scheme of the study and resulted in a set of hypotheses. The study was applied in a community represented by the departments of the Presidency of Al-Mustansiriya University and a sample of (30) individuals. The data were collected through a questionnaire that included (40) questions that dealt with the dimensions of the study and were processed using measures of central tendency and statistical methods when using the electronic calculator within the program (SPSS ver-10). The researchers reached a set of conclusions, the most important of which is the existence of a significant effect of the independent variable, the digitization of mental abilities with its dimensions determined by the Hermann Scale in Entrepreneurial Creativity, according to which the hypothesis was accepted.
Published: 2023
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8. Effect of Porous Media on The Performance Characteristics of a Concentric Vertical Annular Tube

Author: Saad Najeeb Shehab, Hayder Mohammad Jaffal, and Mustafa Fouad Yousif
Subjects: Fluid Flow and Transfer Processes, Materials science, Tube (fluid conveyance), Concentric, Composite material, Porous medium
Published: 2020
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9. Employing Specialized Skills To Develop Smart Systems For Human Resources: An Applied Study In Baghdad Security Dept.

Author: Aziz, Montadher Mahdi, Rahman, Fouad Yousif Abdul, and Majeed, Somaya Abbas
Subjects: ORGANIZATIONAL structure, INFORMATION & communication technologies, WORK environment, DIGITIZATION, PERSONNEL management
Abstract: The research is based on the statement "there is a significant role for employing specialized skills scientifically and accurately and distributing them in a manner that takes into account the achievement of organization and structure, which are compatible with the actual need leads to framing the work scientifically". This kind of employment has an instrumental and prominent role in promoting and developing the smart systems for human resources, their applications and use in a manner coinciding with the specialization required to change all administrative, financial, and security tasks from semi-automated applications to adopting automated digitization. This change would make a qualitative shift in enhancing the position of electronic management as a new launch and building for providing services. The institution under study suffers from obvious neglect and is far from using information and communication technologies and smart systems to enhance the work of administration. The institution also suffers from unlinking internally and externally according to a new digital structure and follow up developments and updates to benefit from it case of a turbulent work environment and new variables that require immediate treatments that reduce time, effort, and cost. In addition, this institution suffers from poor distribution of specialized skills for tasks, responsibilities and duties to match the outputs of those disciplines to transform the traditional routine work into a digital system managed with scientific disciplines and smart systems for human resources. The researcher adopted the digital system in building the intellectual system to determine the research problem and its dimensions, in which the field coexistence of the research community had played a part. [ABSTRACT FROM AUTHOR]
Published: 2022

10. The Use Of NNIS To Develop Mental Abilities A Case Study Of Learning Leaders At Al-Mustansiriya University.

Author: Abdul-Rahman, Fouad Yousif, Majeed, Sumaya Abbas, and Kurji, Sahar Ahmed
Abstract: The study relies on proposing the idea that the use of a neural network information system as one of the types of artificial intelligence has an important role in preparing new models of thinking that support the functions of the human mind and develop its mental skills and abilities. Where many leaders suffer from time management to solve many of the problems that afflict their organizations, which requires the use of electronic digitization and the degree of fear of its use. Where he expressed the problem with a set of questions about the possibility of synchronization between them. The two researchers used the case study and the checklist to explain the philosophical and scientific connection between them, using a sample of "deans, assistants, and heads of scientific departments" from Al-Mustansiriya University as a sample of (100) individuals. The researchers used measures of central tendency and the descriptive analytical method to address the quantitative side. And they reached the most important conclusion: "There is an intellectual awareness among the research sample of the importance of NNIS as a model of thinking that helps and supports the functions of the mind of the individual." [ABSTRACT FROM AUTHOR]
Published: 2022

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

Author: Bailey, Matthew H, Meyerson, William U, Dursi, Lewis Jonathan, Wang, Liang-Bo, Dong, Guanlan, Liang, Wen-Wei, Weerasinghe, Amila, Shantao, Li, Kelso, Sean, Saksena, Gordon, Ellrott, Kyle, Wendl, Michael C, Wheeler, David A, Getz, Gad, Simpson, Jared T, Gerstein, Mark B, Ding, Lirehan, Akbani, Pavana, Anur, Matthew, H Bailey, Alex, Buchanan, Kami, Chiotti, Kyle, Covington, Allison, Creason, Ding, Li, Kyle, Ellrott, Fan, Yu, Steven, Foltz, Gad, Getz, Walker, Hale, David, Haussler, Julian, M Hess, Carolyn, M Hutter, Cyriac, Kandoth, Katayoon, Kasaian, Melpomeni, Kasapi, Dave, Larson, Ignaty, Leshchiner, John, Letaw, Singer, Ma, Michael, D McLellan, Yifei, Men, Gordon, B Mills, Beifang, Niu, Myron, Peto, Amie, Radenbaugh, Sheila, M Reynolds, Gordon, Saksena, Heidi, Sofia, Chip, Stewart, Adam, J Struck, Joshua, M Stuart, Wenyi, Wang, John, N Weinstein, David, A Wheeler, Christopher, K Wong, Liu, Xi, Kai, Ye, Matthias, Bieg, Paul, C Boutros, Ivo, Buchhalter, Adam, P Butler, Ken, Chen, Zechen, Chong, Oliver, Drechsel, Lewis Jonathan Dursi, Roland, Eils, Shadrielle M, G Espiritu, Robert, S Fulton, Shengjie, Gao, Josep L, L Gelpi, Mark, B Gerstein, Santiago, Gonzalez, Ivo, G Gut, Faraz, Hach, Michael, C Heinold, Jonathan, Hinton, Taobo, Hu, Vincent, Huang, Huang, Yi, Barbara, Hutter, David, R Jones, Jongsun, Jung, Natalie, Jäger, Hyung-Lae, Kim, Kortine, Kleinheinz, Sushant, Kumar, Yogesh, Kumar, Christopher, M Lalansingh, Ivica, Letunic, Dimitri, Livitz, Eric, Z Ma, Yosef, E Maruvka, R Jay Mashl, Andrew, Menzies, Ana, Milovanovic, Morten Muhlig Nielsen, Stephan, Ossowski, Nagarajan, Paramasivam, Jakob Skou Pedersen, Marc, D Perry, Montserrat, Puiggròs, Keiran, M Raine, Esther, Rheinbay, Romina, Royo, S Cenk Sahinalp, Iman, Sarrafi, Matthias, Schlesner, Jared, T Simpson, Lucy, Stebbings, Miranda, D Stobbe, Jon, W Teague, Grace, Tiao, David, Torrents, Jeremiah, A Wala, Jiayin, Wang, Sebastian, M Waszak, Joachim, Weischenfeldt, Michael, C Wendl, Johannes, Werner, Zhenggang, Wu, Hong, Xue, Sergei, Yakneen, Takafumi, N Yamaguchi, Venkata, D Yellapantula, Christina, K Yung, Junjun, Zhang, Lauri, A Aaltonen, Federico, Abascal, Adam, Abeshouse, Hiroyuki, Aburatani, David, J Adams, Nishant, Agrawal, Keun Soo Ahn, Sung-Min, Ahn, Hiroshi, Aikata, Rehan, Akbani, Kadir, C Akdemir, Hikmat, Al-Ahmadie, Sultan, T Al-Sedairy, Fatima, Al-Shahrour, Malik, Alawi, Monique, Albert, Kenneth, Aldape, Ludmil, B Alexandrov, Adrian, Ally, Kathryn, Alsop, Eva, G Alvarez, Fernanda, Amary, Samirkumar, B Amin, Brice, Aminou, Ole, Ammerpohl, Matthew, J Anderson, Yeng, Ang, Davide, Antonello, Samuel, Aparicio, Elizabeth, L Appelbaum, Yasuhito, Arai, Axel, Aretz, Koji, Arihiro, Shun-Ichi, Ariizumi, Joshua, Armenia, Laurent, Arnould, Sylvia, Asa, Yassen, Assenov, Gurnit, Atwal, Sietse, Aukema, J Todd Auman, Miriam, R Aure, Philip, Awadalla, Marta, Aymerich, Gary, D Bader, Adrian, Baez-Ortega, Peter, J Bailey, Miruna, Balasundaram, Saianand, Balu, Pratiti, Bandopadhayay, Rosamonde, E Banks, Stefano, Barbi, Andrew, P Barbour, Jonathan, Barenboim, Jill, Barnholtz-Sloan, Hugh, Barr, Elisabet, Barrera, John, Bartlett, Javier, Bartolome, Bassi, Claudio, Oliver, F Bathe, Daniel, Baumhoer, Prashant, Bavi, Stephen, B Baylin, Wojciech, Bazant, Duncan, Beardsmore, Timothy, A Beck, Sam, Behjati, Andreas, Behren, Cindy, Bell, Sergi, Beltran, Christopher, Benz, Andrew, Berchuck, Anke, K Bergmann, Erik, N Bergstrom, Benjamin, P Berman, Daniel, M Berney, Stephan, H Bernhart, Rameen, Beroukhim, Mario, Berrios, Samantha, Bersani, Johanna, Bertl, Miguel, Betancourt, Vinayak, Bhandari, Shriram, G Bhosle, Andrew, V Biankin, Darell, Bigner, Hans, Binder, Ewan, Birney, Michael, Birrer, Nidhan, K Biswas, Bodil, Bjerkehagen, Tom, Bodenheimer, Lori, Boice, Giada, Bonizzato, Johann, S De Bono, Arnoud, Boot, Moiz, S Bootwalla, Ake, Borg, Arndt, Borkhardt, Keith, A Boroevich, Ivan, Borozan, Christoph, Borst, Marcus, Bosenberg, Mattia, Bosio, Jacqueline, Boultwood, Guillaume, Bourque, G Steven Bova, David, T Bowen, Reanne, Bowlby, David D, L Bowtell, Sandrine, Boyault, Rich, Boyce, Jeffrey, Boyd, Alvis, Brazma, Paul, Brennan, Daniel, S Brewer, Arie, B Brinkman, Robert, G Bristow, Russell, R Broaddus, Jane, E Brock, Malcolm, Brock, Annegien, Broeks, Angela, N Brooks, Denise, Brooks, Benedikt, Brors, Søren, Brunak, Timothy J, C Bruxner, Alicia, L Bruzos, Christiane, Buchholz, Susan, Bullman, Hazel, Burke, Birgit, Burkhardt, Kathleen, H Burns, John, Busanovich, Carlos, D Bustamante, Atul, J Butte, Niall, J Byrne, Anne-Lise, Børresen-Dale, Samantha, J Caesar-Johnson, Andy, Cafferkey, Declan, Cahill, Claudia, Calabrese, Carlos, Caldas, Fabien, Calvo, Niedzica, Camacho, Peter, J Campbell, Elias, Campo, Cinzia, Cantù, Shaolong, Cao, Thomas, E Carey, Joana, Carlevaro-Fita, Rebecca, Carlsen, Ivana, Cataldo, Mario, Cazzola, Jonathan, Cebon, Robert, Cerfolio, Dianne, E Chadwick, Dimple, Chakravarty, Don, Chalmers, Calvin Wing Yiu Chan, Kin, Chan, Michelle, Chan-Seng-Yue, Vishal, S Chandan, David, K Chang, Stephen, J Chanock, Lorraine, A Chantrill, Aurélien, Chateigner, Nilanjan, Chatterjee, Kazuaki, Chayama, Hsiao-Wei, Chen, Jieming, Chen, Yiwen, Chen, Zhaohong, Chen, Andrew, D Cherniack, Jeremy, Chien, Yoke-Eng, Chiew, Suet-Feung, Chin, Juok, Cho, Sunghoon, Cho, Jung Kyoon Choi, Wan, Choi, Christine, Chomienne, Su Pin Choo, Angela, Chou, Angelika, N Christ, Elizabeth, L Christie, Eric, Chuah, Carrie, Cibulskis, Kristian, Cibulskis, Sara, Cingarlini, Peter, Clapham, Alexander, Claviez, Sean, Cleary, Nicole, Cloonan, Marek, Cmero, Colin, C Collins, Ashton, A Connor, Susanna, L Cooke, Colin, S Cooper, Leslie, Cope, Corbo, Vincenzo, Matthew, G Cordes, Stephen, M Cordner, Isidro, Cortés-Ciriano, Prue, A Cowin, Brian, Craft, David, Craft, Chad, J Creighton, Yupeng, Cun, Erin, Curley, Ioana, Cutcutache, Karolina, Czajka, Bogdan, Czerniak, Rebecca, A Dagg, Ludmila, Danilova, Maria Vittoria Davi, Natalie, R Davidson, Helen, Davies, Ian, J Davis, Brandi, N Davis-Dusenbery, Kevin, J Dawson, Francisco, M De La Vega, Ricardo De Paoli-Iseppi, Timothy, Defreitas, Angelo, P Dei Tos, Olivier, Delaneau, John, A Demchok, Jonas, Demeulemeester, German, M Demidov, Deniz, Demircioğlu, Nening, M Dennis, Robert, E Denroche, Stefan, C Dentro, Nikita, Desai, Vikram, Deshpande, Amit, G Deshwar, Christine, Desmedt, Jordi, Deu-Pons, Noreen, Dhalla, Neesha, C Dhani, Priyanka, Dhingra, Rajiv, Dhir, Anthony, Dibiase, Klev, Diamanti, Shuai, Ding, Huy, Q Dinh, Luc, Dirix, Harshavardhan, Doddapaneni, Nilgun, Donmez, Michelle, T Dow, Ronny, Drapkin, Ruben, M Drews, Serge, Serge, Tim, Dudderidge, Ana, Dueso-Barroso, Andrew, J Dunford, Michael, Dunn, Fraser, R Duthie, Ken, Dutton-Regester, Jenna, Eagles, Douglas, F Easton, Stuart, Edmonds, Paul, A Edwards, Sandra, E Edwards, Rosalind, A Eeles, Anna, Ehinger, Juergen, Eils, Adel, El-Naggar, Matthew, Eldridge, Serap, Erkek, Georgia, Escaramis, Xavier, Estivill, Dariush, Etemadmoghadam, Jorunn, E Eyfjord, Bishoy, M Faltas, Daiming, Fan, William, C Faquin, Claudiu, Farcas, Matteo, Fassan, Aquila, Fatima, Francesco, Favero, Nodirjon, Fayzullaev, Ina, Felau, Sian, Fereday, Martin, L Ferguson, Vincent, Ferretti, Lars, Feuerbach, Matthew, A Field, J Lynn Fink, Gaetano, Finocchiaro, Cyril, Fisher, Matthew, W Fittall, Anna, Fitzgerald, Rebecca, C Fitzgerald, Adrienne, M Flanagan, Neil, E Fleshner, Paul, Flicek, John, A Foekens, Kwun, M Fong, Nuno, A Fonseca, Christopher, S Foster, Natalie, S Fox, Michael, Fraser, Scott, Frazer, Milana, Frenkel-Morgenstern, William, Friedman, Joan, Frigola, Catrina, C Fronick, Akihiro, Fujimoto, Masashi, Fujita, Masashi, Fukayama, Lucinda, A Fulton, Mayuko, Furuta, P Andrew Futreal, Anja, Füllgrabe, Stacey, B Gabriel, Steven, Gallinger, Carlo, Gambacorti-Passerini, Jianjiong, Gao, Levi, Garraway, Øystein, Garred, Erik, Garrison, Dale, W Garsed, Nils, Gehlenborg, Joshy, George, Daniela, S Gerhard, Clarissa, Gerhauser, Jeffrey, E Gershenwald, Moritz, Gerstung, Mohammed, Ghori, Ronald, Ghossein, Nasra, H Giama, Richard, A Gibbs, Anthony, J Gill, Pelvender, Gill, Dilip, D Giri, Dominik, Glodzik, Vincent, J Gnanapragasam, Maria Elisabeth Goebler, Mary, J Goldman, Carmen, Gomez, Abel, Gonzalez-Perez, Dmitry, A Gordenin, James, Gossage, Kunihito, Gotoh, Ramaswamy, Govindan, Dorthe, Grabau, Janet, S Graham, Robert, C Grant, Anthony, R Green, Eric, Green, Liliana, Greger, Nicola, Grehan, Sonia, Grimaldi, Sean, M Grimmond, Robert, L Grossman, Adam, Grundhoff, Gunes, Gundem, Qianyun, Guo, Manaswi, Gupta, Shailja, Gupta, Marta, Gut, Jonathan, Göke, Gavin, Ha, Andrea, Haake, David, Haan, Siegfried, Haas, Kerstin, Haase, James, E Haber, Nina, Habermann, Syed, Haider, Natsuko, Hama, Freddie, C Hamdy, Anne, Hamilton, Mark, P Hamilton, Leng, Han, George, B Hanna, Martin, Hansmann, Nicholas, J Haradhvala, Olivier, Harismendy, Ivon, Harliwong, Arif, O Harmanci, Eoghan, Harrington, Takanori, Hasegawa, Steve, Hawkins, Shinya, Hayami, Shuto, Hayashi, D Neil Hayes, Stephen, J Hayes, Nicholas, K Hayward, Steven, Hazell, Yao, He, Allison, P Heath, Simon, C Heath, David, Hedley, Apurva, M Hegde, David, I Heiman, Zachary, Heins, Lawrence, E Heisler, Eva, Hellstrom-Lindberg, Mohamed, Helmy, Seong Gu Heo, Austin, J Hepperla, José María Heredia-Genestar, Carl, Herrmann, Peter, Hersey, Holmfridur, Hilmarsdottir, Satoshi, Hirano, Nobuyoshi, Hiraoka, Katherine, A Hoadley, Asger, Hobolth, Ermin, Hodzic, Jessica, I Hoell, Steve, Hoffmann, Oliver, Hofmann, Andrea, Holbrook, Aliaksei, Z Holik, Michael, A Hollingsworth, Oliver, Holmes, Robert, A Holt, Chen, Hong, Eun Pyo Hong, Jongwhi, H Hong, Gerrit, K Hooijer, Henrik, Hornshøj, Fumie, Hosoda, Yong, Hou, Volker, Hovestadt, William, Howat, Alan, P Hoyle, Ralph, H Hruban, Jianhong, Hu, Xing, Hua, Kuan-Lin, Huang, Mei, Huang, Mi Ni Huang, Wolfgang, Huber, Thomas, J Hudson, Michael, Hummel, Jillian, A Hung, David, Huntsman, Ted, R Hupp, Jason, Huse, Matthew, R Huska, Daniel, Hübschmann, Christine, A Iacobuzio-Donahue, Charles David Imbusch, Marcin, Imielinski, Seiya, Imoto, William, B Isaacs, Keren, Isaev, Shumpei, Ishikawa, Murat, Iskar, M Ashiqul Islam, S, Michael, Ittmann, Sinisa, Ivkovic, Jose M, G Izarzugaza, Jocelyne, Jacquemier, Valerie, Jakrot, Nigel, B Jamieson, Gun Ho Jang, Se Jin Jang, Joy, C Jayaseelan, Reyka, Jayasinghe, Stuart, R Jefferys, Karine, Jegalian, Jennifer, L Jennings, Seung-Hyup, Jeon, Lara, Jerman, Yuan, Ji, Wei, Jiao, Peter, A Johansson, Amber, L Johns, Jeremy, Johns, Rory, Johnson, Todd, A Johnson, Clemency, Jolly, Yann, Joly, Jon, G Jonasson, Corbin, D Jones, David T, W Jones, Nic, Jones, Steven J, M Jones, Jos, Jonkers, Young Seok Ju, Hartmut, Juhl, Malene, Juul, Randi Istrup Juul, Sissel, Juul, Rolf, Kabbe, Andre, Kahles, Abdullah, Kahraman, Vera, B Kaiser, Hojabr, Kakavand, Sangeetha, Kalimuthu, Christof von Kalle, Koo Jeong Kang, Katalin, Karaszi, Beth, Karlan, Rosa, Karlić, Dennis, Karsch, Karin, S Kassahn, Hitoshi, Katai, Mamoru, Kato, Hiroto, Katoh, Yoshiiku, Kawakami, Jonathan, D Kay, Stephen, H Kazakoff, Marat, D Kazanov, Maria, Keays, Electron, Kebebew, Richard, F Kefford, Manolis, Kellis, James, G Kench, Catherine, J Kennedy, Jules N, A Kerssemakers, David, Khoo, Vincent, Khoo, Narong, Khuntikeo, Ekta, Khurana, Helena, Kilpinen, Hark Kyun Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jaegil, Kim, Jihoon, Kim, Jong, K Kim, Youngwook, Kim, Tari, A King, Wolfram, Klapper, Leszek, J Klimczak, Stian, Knappskog, Michael, Kneba, Bartha, M Knoppers, Youngil, Koh, Jan, Komorowski, Daisuke, Komura, Mitsuhiro, Komura, Kong, Gu, Marcel, Kool, Jan, O Korbel, Viktoriya, Korchina, Andrey, Korshunov, Michael, Koscher, Roelof, Koster, Zsofia, Kote-Jarai, Antonios, Koures, Milena, Kovacevic, Barbara, Kremeyer, Helene, Kretzmer, Markus, Kreuz, Savitri, Krishnamurthy, Dieter, Kube, Kiran, Kumar, Pardeep, Kumar, Ritika, Kundra, Kirsten, Kübler, Ralf, Küppers, Jesper, Lagergren, Phillip, H Lai, Peter, W Laird, Sunil, R Lakhani, Emilie, Lalonde, Fabien, C Lamaze, Adam, Lambert, Eric, Lander, Pablo, Landgraf, Landoni, Luca, Anita, Langerød, Andrés, Lanzós, Denis, Larsimont, Erik, Larsson, Mark, Lathrop, Loretta M, S Lau, Chris, Lawerenz, Rita, T Lawlor, Michael, S Lawrence, Alexander, J Lazar, Xuan, Le, Darlene, Lee, Donghoon, Lee, Eunjung Alice Lee, Hee Jin Lee, Jake June-Koo Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael Lee, Henry, Lee-Six, Kjong-Van, Lehmann, Hans, Lehrach, Dido, Lenze, Conrad, R Leonard, Daniel, A Leongamornlert, Louis, Letourneau, Douglas, A Levine, Lora, Lewis, Tim, Ley, Chang, Li, Constance, H Li, Haiyan Irene Li, Jun, Li, Lin, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Li, Yilong, Li, Han, Liang, Sheng-Ben, Liang, Peter, Lichter, Pei, Lin, Ziao, Lin, M Linehan, W, Ole Christian Lingjærde, Dongbing, Liu, Eric Minwei Liu, Fei-Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Liu, Julie, Livingstone, Naomi, Livni, Lucas, Lochovsky, Markus, Loeffler, Georgina, V Long, Armando, Lopez-Guillermo, Shaoke, Lou, David, N Louis, Laurence, B Lovat, Yiling, Lu, Yong-Jie, Lu, Youyong, Lu, Luchini, Claudio, Ilinca, Lungu, Xuemei, Luo, Hayley, J Luxton, Andy, G Lynch, Lisa, Lype, Cristina, López, Carlos, López-Otín, Yussanne, Ma, Gaetan, Macgrogan, Shona, Macrae, Geoff, Macintyre, Tobias, Madsen, Kazuhiro, Maejima, Andrea, Mafficini, Dennis, T Maglinte, Arindam, Maitra, Partha, P Majumder, Luca, Malcovati, Salem, Malikic, Malleo, Giuseppe, Graham, J Mann, Luisa, Mantovani-Löffler, Kathleen, Marchal, Giovanni, Marchegiani, Elaine, R Mardis, Adam, A Margolin, Maximillian, G Marin, Florian, Markowetz, Julia, Markowski, Jeffrey, Marks, Tomas, Marques-Bonet, Marco, A Marra, Luke, Marsden, John W, M Martens, Sancha, Martin, Jose, I Martin-Subero, Iñigo, Martincorena, Alexander, Martinez-Fundichely, Charlie, E Massie, Thomas, J Matthew, Lucy, Matthews, Erik, Mayer, Simon, Mayes, Michael, Mayo, Faridah, Mbabaali, Karen, Mccune, Ultan, Mcdermott, Patrick, D McGillivray, John, D McPherson, John, R McPherson, Treasa, A McPherson, Samuel, R Meier, Alice, Meng, Shaowu, Meng, Neil, D Merrett, Sue, Merson, Matthew, Meyerson, William, U Meyerson, Piotr, A Mieczkowski, George, L Mihaiescu, Sanja, Mijalkovic, Ana Mijalkovic Mijalkovic-Lazic, Tom, Mikkelsen, Milella, Michele, Linda, Mileshkin, Christopher, A Miller, David, K Miller, Jessica, K Miller, Sarah, Minner, Marco, Miotto, Gisela Mir Arnau, Lisa, Mirabello, Chris, Mitchell, Thomas, J Mitchell, Satoru, Miyano, Naoki, Miyoshi, Shinichi, Mizuno, Fruzsina, Molnár-Gábor, Malcolm, J Moore, Richard, A Moore, Sandro, Morganella, Quaid, D Morris, Carl, Morrison, Lisle, E Mose, Catherine, D Moser, Ferran, Muiños, Loris, Mularoni, Andrew, J Mungall, Karen, Mungall, Elizabeth, A Musgrove, Ville, Mustonen, David, Mutch, Francesc, Muyas, Donna, M Muzny, Alfonso, Muñoz, Jerome, Myers, Ola, Myklebost, Peter, Möller, Genta, Nagae, Adnan, M Nagrial, Hardeep, K Nahal-Bose, Hitoshi, Nakagama, Hidewaki, Nakagawa, Hiromi, Nakamura, Toru, Nakamura, Kaoru, Nakano, Tannistha, Nandi, Jyoti, Nangalia, Mia, Nastic, Arcadi, Navarro, Fabio C, P Navarro, David, E Neal, Gerd, Nettekoven, Felicity, Newell, Steven, J Newhouse, Yulia, Newton, Alvin Wei Tian Ng, Anthony, Ng, Jonathan, Nicholson, David, Nicol, Yongzhan, Nie, G Petur Nielsen, Serena, Nik-Zainal, Michael, S Noble, Katia, Nones, Paul, A Northcott, Faiyaz, Notta, Brian, D O'Connor, Peter, O'Donnell, Maria, O'Donovan, Sarah, O'Meara, Brian Patrick O'Neill, J Robert O'Neill, David, Ocana, Angelica, Ochoa, Layla, Oesper, Christopher, Ogden, Hideki, Ohdan, Kazuhiro, Ohi, Lucila, Ohno-Machado, Karin, A Oien, Akinyemi, I Ojesina, Hidenori, Ojima, Takuji, Okusaka, Larsson, Omberg, Choon Kiat Ong, German, Ott, F Francis Ouellette, B, Christine, P'Ng, Marta, Paczkowska, Paiella, Salvatore, Chawalit, Pairojkul, Marina, Pajic, Qiang, Pan-Hammarström, Elli, Papaemmanuil, Irene, Papatheodorou, Ji Wan Park, Joong-Won, Park, Keunchil, Park, Kiejung, Park, Peter, J Park, Joel, S Parker, Simon, L Parsons, Harvey, Pass, Danielle, Pasternack, Alessandro, Pastore, Ann-Marie, Patch, Iris, Pauporté, Antonio, Pea, John, V Pearson, Chandra Sekhar Pedamallu, Paolo, Pederzoli, Martin, Peifer, Nathan, A Pennell, Charles, M Perou, Gloria, M Petersen, Nicholas, Petrelli, Robert, Petryszak, Stefan, M Pfister, Mark, Phillips, Oriol, Pich, Hilda, A Pickett, Todd, D Pihl, Nischalan, Pillay, Sarah, Pinder, Mark, Pinese, Andreia, V Pinho, Esa, Pitkänen, Xavier, Pivot, Elena, Piñeiro-Yáñez, Laura, Planko, Christoph, Plass, Paz, Polak, Tirso, Pons, Irinel, Popescu, Olga, Potapova, Aparna, Prasad, Shaun, R Preston, Manuel, Prinz, Antonia, L Pritchard, Stephenie, D Prokopec, Elena, Provenzano, Xose, S Puente, Sonia, Puig, Sergio, Pulido-Tamayo, Gulietta, M Pupo, Colin, A Purdie, Michael, C Quinn, Raquel, Rabionet, Janet, S Rader, Bernhard, Radlwimmer, Petar, Radovic, Benjamin, Raeder, Manasa, Ramakrishna, Kamna, Ramakrishnan, Suresh, Ramalingam, Benjamin, J Raphael, W Kimryn Rathmell, Tobias, Rausch, Guido, Reifenberger, Jüri, Reimand, Jorge, Reis-Filho, Victor, Reuter, Iker, Reyes-Salazar, Matthew, A Reyna, Yasser, Riazalhosseini, Andrea, L Richardson, Julia, Richter, Matthew, Ringel, Markus, Ringnér, Yasushi, Rino, Karsten, Rippe, Jeffrey, Roach, Lewis, R Roberts, Nicola, D Roberts, Steven, A Roberts, A Gordon Robertson, Alan, J Robertson, Javier Bartolomé Rodriguez, Bernardo, Rodriguez-Martin, F Germán Rodríguez-González, Michael H, A Roehrl, Marius, Rohde, Hirofumi, Rokutan, Gilles, Romieu, Ilse, Rooman, Tom, Roques, Daniel, Rosebrock, Mara, Rosenberg, Philip, C Rosenstiel, Andreas, Rosenwald, Edward, W Rowe, Steven, G Rozen, Yulia, Rubanova, Mark, A Rubin, Carlota, Rubio-Perez, Vasilisa, A Rudneva, Borislav, C Rusev, Ruzzenente, Andrea, Gunnar, Rätsch, Radhakrishnan, Sabarinathan, Veronica, Y Sabelnykova, Sara, Sadeghi, Natalie, Saini, Mihoko, Saito-Adachi, Adriana, Salcedo, Roberto, Salgado, Leonidas, Salichos, Richard, Sallari, Charles, Saller, Salvia, Roberto, Michelle, Sam, Jaswinder, S Samra, Francisco, Sanchez-Vega, Chris, Sander, Grant, Sanders, Rajiv, Sarin, Aya, Sasaki-Oku, Torill, Sauer, Guido, Sauter, Robyn P, M Saw, Maria, Scardoni, Christopher, J Scarlett, Scarpa, Aldo, Ghislaine, Scelo, Dirk, Schadendorf, Jacqueline, E Schein, Markus, B Schilhabel, Thorsten, Schlomm, Heather, K Schmidt, Sarah-Jane, Schramm, Stefan, Schreiber, Nikolaus, Schultz, Steven, E Schumacher, Roland, F Schwarz, Richard, A Scolyer, David, Scott, Ralph, Scully, Raja, Seethala, Ayellet, V Segre, Iris, Selander, Colin, A Semple, Yasin, Senbabaoglu, Subhajit, Sengupta, Elisabetta, Sereni, Stefano, Serra, Dennis, C Sgroi, Mark, Shackleton, Nimish, C Shah, Sagedeh, Shahabi, Catherine, A Shang, Ping, Shang, Ofer, Shapira, Troy, Shelton, Ciyue, Shen, Hui, Shen, Rebecca, Shepherd, Ruian, Shi, Yan, Shi, Yu-Jia, Shiah, Tatsuhiro, Shibata, Juliann, Shih, Eigo, Shimizu, Kiyo, Shimizu, Seung Jun Shin, Yuichi, Shiraishi, Tal, Shmaya, Ilya, Shmulevich, Solomon, I Shorser, Charles, Short, Raunak, Shrestha, Suyash, S Shringarpure, Craig, Shriver, Shimin, Shuai, Nikos, Sidiropoulos, Reiner, Siebert, Anieta, M Sieuwerts, Lina, Sieverling, Sabina, Signoretti, Katarzyna, O Sikora, Michele, Simbolo, Ronald, Simon, Janae, V Simons, Peter, T Simpson, Samuel, Singer, Nasa, Sinnott-Armstrong, Payal, Sipahimalani, Tara, J Skelly, Marcel, Smid, Jaclyn, Smith, Karen, Smith-McCune, Nicholas, D Socci, Heidi, J Sofia, Matthew, G Soloway, Lei, Song, Anil, K Sood, Sharmila, Sothi, Christos, Sotiriou, Cameron, M Soulette, Paul, N Span, Paul, T Spellman, Sperandio, Nicola, Andrew, J Spillane, Oliver, Spiro, Jonathan, Spring, Johan, Staaf, Peter, F Stadler, Peter, Staib, Stefan, G Stark, Ólafur Andri Stefánsson, Oliver, Stegle, Lincoln, D Stein, Alasdair, Stenhouse, Stephan, Stilgenbauer, Michael, R Stratton, Jonathan, R Stretch, Henk, G Stunnenberg, Hong, Su, Xiaoping, Su, Ren, X Sun, Stephanie, Sungalee, Hana, Susak, Akihiro, Suzuki, Fred, Sweep, Monika, Szczepanowski, Holger, Sültmann, Takashi, Yugawa, Angela, Tam, David, Tamborero, Benita Kiat Tee Tan, Donghui, Tan, Patrick, Tan, Hiroko, Tanaka, Hirokazu, Taniguchi, Tomas, J Tanskanen, Maxime, Tarabichi, Roy, Tarnuzzer, Patrick, Tarpey, Morgan, L Taschuk, Kenji, Tatsuno, Simon, Tavaré, Darrin, F Taylor, Amaro, Taylor-Weiner, Bin Tean Teh, Varsha, Tembe, Javier, Temes, Kevin, Thai, Sarah, P Thayer, Nina, Thiessen, Gilles, Thomas, Sarah, Thomas, Alan, Thompson, Alastair, M Thompson, John, F Thompson, R Houston Thompson, Heather, Thorne, Leigh, B Thorne, Adrian, Thorogood, Nebojsa, Tijanic, Lee, E Timms, Roberto, Tirabosco, Marta, Tojo, Stefania, Tommasi, Christopher, W Toon, Umut, H Toprak, Giampaolo, Tortora, Jörg, Tost, Yasushi, Totoki, David, Townend, Nadia, Traficante, Isabelle, Treilleux, Jean-Rémi, Trotta, Lorenz H, P Trümper, Ming, Tsao, Tatsuhiko, Tsunoda, Jose M, C Tubio, Olga, Tucker, Richard, Turkington, Daniel, J Turner, Andrew, Tutt, Masaki, Ueno, Naoto, T Ueno, Christopher, Umbricht, Husen, M Umer, Timothy, J Underwood, Lara, Urban, Tomoko, Urushidate, Tetsuo, Ushiku, Liis, Uusküla-Reimand, Alfonso, Valencia, David, J Van Den Berg, Steven Van Laere, Peter Van Loo, Erwin, G Van Meir, Gert, G Van den Eynden, Theodorus Van der Kwast, Naveen, Vasudev, Miguel, Vazquez, Ravikiran, Vedururu, Umadevi, Veluvolu, Shankar, Vembu, Lieven P, C Verbeke, Peter, Vermeulen, Clare, Verrill, Alain, Viari, David, Vicente, Caterina, Vicentini, K Vijay Raghavan, Juris, Viksna, Ricardo, E Vilain, Izar, Villasante, Anne, Vincent-Salomon, Tapio, Visakorpi, Douglas, Voet, Paresh, Vyas, Ignacio, Vázquez-García, Nick, M Waddell, Nicola, Waddell, Claes, Wadelius, Lina, Wadi, Rabea, Wagener, Jian, Wang, Linghua, Wang, Wang, Qi, Yumeng, Wang, Zhining, Wang, Paul, M Waring, Hans-Jörg, Warnatz, Jonathan, Warrell, Anne, Y Warren, David, C Wedge, Dieter, Weichenhan, Paul, Weinberger, Daniel, J Weisenberger, Ian, Welch, Justin, P Whalley, Hayley, C Whitaker, Dennis, Wigle, Matthew, D Wilkerson, Ashley, Williams, James, S Wilmott, Gavin, W Wilson, Julie, M Wilson, Richard, K Wilson, Boris, Winterhoff, Jeffrey, A Wintersinger, Maciej, Wiznerowicz, Stephan, Wolf, Bernice, H Wong, Tina, Wong, Winghing, Wong, Youngchoon, Woo, Scott, Wood, Bradly, G Wouters, Adam, J Wright, Derek, W Wright, Mark, H Wright, Chin-Lee, Wu, Dai-Ying, Wu, Guanming, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Tian, Xia, Qian, Xiang, Xiao, Xiao, Rui, Xing, Heng, Xiong, Qinying, Xu, Yanxun, Xu, Shinichi, Yachida, Rui, Yamaguchi, Masakazu, Yamamoto, Shogo, Yamamoto, Hiroki, Yamaue, Fan, Yang, Huanming, Yang, Jean, Y Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yang, Xiaotong, Yao, Marie-Laure, Yaspo, Lucy, Yates, Christina, Yau, Chen, Ye, Christopher, J Yoon, Sung-Soo, Yoon, Fouad, Yousif, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yu, Yuan, Ke, Yuan, Yuan, Denis, Yuen, Olga, Zaikova, Jorge, Zamora, Marc, Zapatka, Jean, C Zenklusen, Thorsten, Zenz, Nikolajs, Zeps, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhang, Zhongming, Zhao, Liangtao, Zheng, Xiuqing, Zheng, Wanding, Zhou, Yong, Zhou, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zhu, Lihua, Zou, Xueqing, Zou, Anna, Defazio, Nicholas van As, Carolien H, M van Deurzen, Marc, J van de Vijver, L Van't Veer, Christian von Mering, Medical Oncology, Pathology, Bailey, Matthew H. [0000-0003-4526-9727], Dursi, Lewis Jonathan [0000-0002-4697-798X], Wang, Liang-Bo [0000-0001-6977-9348], Dong, Guanlan [0000-0002-4747-6036], Weerasinghe, Amila [0000-0003-3568-5823], Li, Shantao [0000-0002-5440-2780], Saksena, Gordon [0000-0001-6630-7935], Ellrott, Kyle [0000-0002-6573-5900], Wheeler, David A. [0000-0002-9056-6299], Getz, Gad [0000-0002-0936-0753], Gerstein, Mark B. [0000-0002-9746-3719], Apollo - University of Cambridge Repository, CCA - Cancer biology and immunology, Graduate School, Laboratory Genetic Metabolic Diseases, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Bailey, M, Meyerson, W, Dursi, L, Wang, L, Dong, G, Liang, W, Weerasinghe, A, Li, S, Kelso, S, Akbani, R, Anur, P, Buchanan, A, Chiotti, K, Covington, K, Creason, A, Ding, L, Ellrott, K, Fan, Y, Foltz, S, Getz, G, Hale, W, Haussler, D, Hess, J, Hutter, C, Kandoth, C, Kasaian, K, Kasapi, M, Larson, D, Leshchiner, I, Letaw, J, Ma, S, Mclellan, M, Men, Y, Mills, G, Niu, B, Peto, M, Radenbaugh, A, Reynolds, S, Saksena, G, Sofia, H, Stewart, C, Struck, A, Stuart, J, Wang, W, Weinstein, J, Wheeler, D, Wong, C, Xi, L, Ye, K, Bieg, M, Boutros, P, Buchhalter, I, Butler, A, Chen, K, Chong, Z, Drechsel, O, Jonathan Dursi, L, Eils, R, Espiritu, S, Fulton, R, Gao, S, Gelpi, J, Gerstein, M, Gonzalez, S, Gut, I, Hach, F, Heinold, M, Hinton, J, Hu, T, Huang, V, Huang, Y, Hutter, B, Jones, D, Jung, J, Jager, N, Kim, H, Kleinheinz, K, Kumar, S, Kumar, Y, Lalansingh, C, Letunic, I, Livitz, D, Ma, E, Maruvka, Y, Mashl, R, Menzies, A, Milovanovic, A, Nielsen, M, Ossowski, S, Paramasivam, N, Pedersen, J, Perry, M, Puiggros, M, Raine, K, Rheinbay, E, Royo, R, Sahinalp, S, Sarrafi, I, Schlesner, M, Simpson, J, Stebbings, L, Stobbe, M, Teague, J, Tiao, G, Torrents, D, Wala, J, Wang, J, Waszak, S, Weischenfeldt, J, Wendl, M, Werner, J, Wu, Z, Xue, H, Yakneen, S, Yamaguchi, T, Yellapantula, V, Yung, C, Zhang, J, Aaltonen, L, Abascal, F, Abeshouse, A, Aburatani, H, Adams, D, Agrawal, N, Ahn, K, Ahn, S, Aikata, H, Akdemir, K, Al-Ahmadie, H, Al-Sedairy, S, Al-Shahrour, F, Alawi, M, Albert, M, Aldape, K, Alexandrov, L, Ally, A, Alsop, K, Alvarez, E, Amary, F, Amin, S, Aminou, B, Ammerpohl, O, Anderson, M, Ang, Y, Antonello, D, Aparicio, S, Appelbaum, E, Arai, Y, Aretz, A, Arihiro, K, Ariizumi, S, Armenia, J, Arnould, L, Asa, S, Assenov, Y, Atwal, G, Aukema, S, Auman, J, Aure, M, Awadalla, P, Aymerich, M, Bader, G, Baez-Ortega, A, Bailey, P, Balasundaram, M, Balu, S, Bandopadhayay, P, Banks, R, Barbi, S, Barbour, A, Barenboim, J, Barnholtz-Sloan, J, Barr, H, Barrera, E, Bartlett, J, Bartolome, J, Bassi, C, Bathe, O, Baumhoer, D, Bavi, P, Baylin, S, Bazant, W, Beardsmore, D, Beck, T, Behjati, S, Behren, A, Bell, C, Beltran, S, Benz, C, Berchuck, A, Bergmann, A, Bergstrom, E, Berman, B, Berney, D, Bernhart, S, Beroukhim, R, Berrios, M, Bersani, S, Bertl, J, Betancourt, M, Bhandari, V, Bhosle, S, Biankin, A, Bigner, D, Binder, H, Birney, E, Birrer, M, Biswas, N, Bjerkehagen, B, Bodenheimer, T, Boice, L, Bonizzato, G, De Bono, J, Boot, A, Bootwalla, M, Borg, A, Borkhardt, A, Boroevich, K, Borozan, I, Borst, C, Bosenberg, M, Bosio, M, Boultwood, J, Bourque, G, Bova, G, Bowen, D, Bowlby, R, Bowtell, D, Boyault, S, Boyce, R, Boyd, J, Brazma, A, Brennan, P, Brewer, D, Brinkman, A, Bristow, R, Broaddus, R, Brock, J, Brock, M, Broeks, A, Brooks, A, Brooks, D, Brors, B, Brunak, S, Bruxner, T, Bruzos, A, Buchholz, C, Bullman, S, Burke, H, Burkhardt, B, Burns, K, Busanovich, J, Bustamante, C, Butte, A, Byrne, N, Borresen-Dale, A, Caesar-Johnson, S, Cafferkey, A, Cahill, D, Calabrese, C, Caldas, C, Calvo, F, Camacho, N, Campbell, P, Campo, E, Cantu, C, Cao, S, Carey, T, Carlevaro-Fita, J, Carlsen, R, Cataldo, I, Cazzola, M, Cebon, J, Cerfolio, R, Chadwick, D, Chakravarty, D, Chalmers, D, Chan, C, Chan, K, Chan-Seng-Yue, M, Chandan, V, Chang, D, Chanock, S, Chantrill, L, Chateigner, A, Chatterjee, N, Chayama, K, Chen, H, Chen, J, Chen, Y, Chen, Z, Cherniack, A, Chien, J, Chiew, Y, Chin, S, Cho, J, Cho, S, Choi, J, Choi, W, Chomienne, C, Choo, S, Chou, A, Christ, A, Christie, E, Chuah, E, Cibulskis, C, Cibulskis, K, Cingarlini, S, Clapham, P, Claviez, A, Cleary, S, Cloonan, N, Cmero, M, Collins, C, Connor, A, Cooke, S, Cooper, C, Cope, L, Corbo, V, Cordes, M, Cordner, S, Cortes-Ciriano, I, Cowin, P, Craft, B, Craft, D, Creighton, C, Cun, Y, Curley, E, Cutcutache, I, Czajka, K, Czerniak, B, Dagg, R, Danilova, L, Davi, M, Davidson, N, Davies, H, Davis, I, Davis-Dusenbery, B, Dawson, K, De La Vega, F, De Paoli-Iseppi, R, Defreitas, T, Dei Tos, A, Delaneau, O, Demchok, J, Demeulemeester, J, Demidov, G, Demircioglu, D, Dennis, N, Denroche, R, Dentro, S, Desai, N, Deshpande, V, Deshwar, A, Desmedt, C, Deu-Pons, J, Dhalla, N, Dhani, N, Dhingra, P, Dhir, R, Dibiase, A, Diamanti, K, Ding, S, Dinh, H, Dirix, L, Doddapaneni, H, Donmez, N, Dow, M, Drapkin, R, Drews, R, Serge, S, Dudderidge, T, Dueso-Barroso, A, Dunford, A, Dunn, M, Duthie, F, Dutton-Regester, K, Eagles, J, Easton, D, Edmonds, S, Edwards, P, Edwards, S, Eeles, R, Ehinger, A, Eils, J, El-Naggar, A, Eldridge, M, Erkek, S, Escaramis, G, Estivill, X, Etemadmoghadam, D, Eyfjord, J, Faltas, B, Fan, D, Faquin, W, Farcas, C, Fassan, M, Fatima, A, Favero, F, Fayzullaev, N, Felau, I, Fereday, S, Ferguson, M, Ferretti, V, Feuerbach, L, Field, M, Fink, J, Finocchiaro, G, Fisher, C, Fittall, M, Fitzgerald, A, Fitzgerald, R, Flanagan, A, Fleshner, N, Flicek, P, Foekens, J, Fong, K, Fonseca, N, Foster, C, Fox, N, Fraser, M, Frazer, S, Frenkel-Morgenstern, M, Friedman, W, Frigola, J, Fronick, C, Fujimoto, A, Fujita, M, Fukayama, M, Fulton, L, Furuta, M, Futreal, P, Fullgrabe, A, Gabriel, S, Gallinger, S, Gambacorti Passerini, C, Gao, J, Garraway, L, Garred, O, Garrison, E, Garsed, D, Gehlenborg, N, George, J, Gerhard, D, Gerhauser, C, Gershenwald, J, Gerstung, M, Ghori, M, Ghossein, R, Giama, N, Gibbs, R, Gill, A, Gill, P, Giri, D, Glodzik, D, Gnanapragasam, V, Goebler, M, Goldman, M, Gomez, C, Gonzalez-Perez, A, Gordenin, D, Gossage, J, Gotoh, K, Govindan, R, Grabau, D, Graham, J, Grant, R, Green, A, Green, E, Greger, L, Grehan, N, Grimaldi, S, Grimmond, S, Grossman, R, Grundhoff, A, Gundem, G, Guo, Q, Gupta, M, Gupta, S, Gut, M, Goke, J, Ha, G, Haake, A, Haan, D, Haas, S, Haase, K, Haber, J, Habermann, N, Haider, S, Hama, N, Hamdy, F, Hamilton, A, Hamilton, M, Han, L, Hanna, G, Hansmann, M, Haradhvala, N, Harismendy, O, Harliwong, I, Harmanci, A, Harrington, E, Hasegawa, T, Hawkins, S, Hayami, S, Hayashi, S, Hayes, D, Hayes, S, Hayward, N, Hazell, S, He, Y, Heath, A, Heath, S, Hedley, D, Hegde, A, Heiman, D, Heins, Z, Heisler, L, Hellstrom-Lindberg, E, Helmy, M, Heo, S, Hepperla, A, Heredia-Genestar, J, Herrmann, C, Hersey, P, Hilmarsdottir, H, Hirano, S, Hiraoka, N, Hoadley, K, Hobolth, A, Hodzic, E, Hoell, J, Hoffmann, S, Hofmann, O, Holbrook, A, Holik, A, Hollingsworth, M, Holmes, O, Holt, R, Hong, C, Hong, E, Hong, J, Hooijer, G, Hornshoj, H, Hosoda, F, Hou, Y, Hovestadt, V, Howat, W, Hoyle, A, Hruban, R, Hu, J, Hua, X, Huang, K, Huang, M, Huber, W, Hudson, T, Hummel, M, Hung, J, Huntsman, D, Hupp, T, Huse, J, Huska, M, Hubschmann, D, Iacobuzio-Donahue, C, Imbusch, C, Imielinski, M, Imoto, S, Isaacs, W, Isaev, K, Ishikawa, S, Iskar, M, Islam, S, Ittmann, M, Ivkovic, S, Izarzugaza, J, Jacquemier, J, Jakrot, V, Jamieson, N, Jang, G, Jang, S, Jayaseelan, J, Jayasinghe, R, Jefferys, S, Jegalian, K, Jennings, J, Jeon, S, Jerman, L, Ji, Y, Jiao, W, Johansson, P, Johns, A, Johns, J, Johnson, R, Johnson, T, Jolly, C, Joly, Y, Jonasson, J, Jones, C, Jones, N, Jones, S, Jonkers, J, Ju, Y, Juhl, H, Juul, M, Juul, R, Juul, S, Kabbe, R, Kahles, A, Kahraman, A, Kaiser, V, Kakavand, H, Kalimuthu, S, von Kalle, C, Kang, K, Karaszi, K, Karlan, B, Karlic, R, Karsch, D, Kassahn, K, Katai, H, Kato, M, Katoh, H, Kawakami, Y, Kay, J, Kazakoff, S, Kazanov, M, Keays, M, Kebebew, E, Kefford, R, Kellis, M, Kench, J, Kennedy, C, Kerssemakers, J, Khoo, D, Khoo, V, Khuntikeo, N, Khurana, E, Kilpinen, H, Kim, J, Kim, Y, King, T, Klapper, W, Klimczak, L, Knappskog, S, Kneba, M, Knoppers, B, Koh, Y, Jan, K, Komura, D, Komura, M, Kong, G, Kool, M, Korbel, J, Korchina, V, Korshunov, A, Koscher, M, Koster, R, Kote-Jarai, Z, Koures, A, Kovacevic, M, Kremeyer, B, Kretzmer, H, Kreuz, M, Krishnamurthy, S, Kube, D, Kumar, K, Kumar, P, Kundra, R, Kubler, K, Kuppers, R, Lagergren, J, Lai, P, Laird, P, Lakhani, S, Lalonde, E, Lamaze, F, Lambert, A, Lander, E, Landgraf, P, Landoni, L, Langerod, A, Lanzos, A, Larsimont, D, Larsson, E, Lathrop, M, Lau, L, Lawerenz, C, Lawlor, R, Lawrence, M, Lazar, A, Le, X, Lee, D, Lee, E, Lee, H, Lee, J, Lee, M, Lee-Six, H, Lehmann, K, Lehrach, H, Lenze, D, Leonard, C, Leongamornlert, D, Letourneau, L, Levine, D, Lewis, L, Ley, T, Li, C, Li, H, Li, J, Li, L, Li, X, Li, Y, Liang, H, Liang, S, Lichter, P, Lin, P, Lin, Z, Linehan, W, Lingjaerde, O, Liu, D, Liu, E, Liu, F, Liu, J, Liu, X, Livingstone, J, Livni, N, Lochovsky, L, Loeffler, M, Long, G, Lopez-Guillermo, A, Lou, S, Louis, D, Lovat, L, Lu, Y, Luchini, C, Lungu, I, Luo, X, Luxton, H, Lynch, A, Lype, L, Lopez, C, Lopez-Otin, C, Ma, Y, Macgrogan, G, Macrae, S, Macintyre, G, Madsen, T, Maejima, K, Mafficini, A, Maglinte, D, Maitra, A, Majumder, P, Malcovati, L, Malikic, S, Malleo, G, Mann, G, Mantovani-Loffler, L, Marchal, K, Marchegiani, G, Mardis, E, Margolin, A, Marin, M, Markowetz, F, Markowski, J, Marks, J, Marques-Bonet, T, Marra, M, Marsden, L, Martens, J, Martin, S, Martin-Subero, J, Martincorena, I, Martinez-Fundichely, A, Massie, C, Matthew, T, Matthews, L, Mayer, E, Mayes, S, Mayo, M, Mbabaali, F, Mccune, K, Mcdermott, U, Mcgillivray, P, Mcpherson, J, Mcpherson, T, Meier, S, Meng, A, Meng, S, Merrett, N, Merson, S, Meyerson, M, Mieczkowski, P, Mihaiescu, G, Mijalkovic, S, Mijalkovic-Lazic, A, Mikkelsen, T, Milella, M, Mileshkin, L, Miller, C, Miller, D, Miller, J, Minner, S, Miotto, M, Arnau, G, Mirabello, L, Mitchell, C, Mitchell, T, Miyano, S, Miyoshi, N, Mizuno, S, Molnar-Gabor, F, Moore, M, Moore, R, Morganella, S, Morris, Q, Morrison, C, Mose, L, Moser, C, Muinos, F, Mularoni, L, Mungall, A, Mungall, K, Musgrove, E, Mustonen, V, Mutch, D, Muyas, F, Muzny, D, Munoz, A, Myers, J, Myklebost, O, Moller, P, Nagae, G, Nagrial, A, Nahal-Bose, H, Nakagama, H, Nakagawa, H, Nakamura, H, Nakamura, T, Nakano, K, Nandi, T, Nangalia, J, Nastic, M, Navarro, A, Navarro, F, Neal, D, Nettekoven, G, Newell, F, Newhouse, S, Newton, Y, Ng, A, Nicholson, J, Nicol, D, Nie, Y, Nielsen, G, Nik-Zainal, S, Noble, M, Nones, K, Northcott, P, Notta, F, O'Connor, B, O'Donnell, P, O'Donovan, M, O'Meara, S, O'Neill, B, O'Neill, J, Ocana, D, Ochoa, A, Oesper, L, Ogden, C, Ohdan, H, Ohi, K, Ohno-Machado, L, Oien, K, Ojesina, A, Ojima, H, Okusaka, T, Omberg, L, Ong, C, Ott, G, Ouellette, B, P'Ng, C, Paczkowska, M, Paiella, S, Pairojkul, C, Pajic, M, Pan-Hammarstrom, Q, Papaemmanuil, E, Papatheodorou, I, Park, J, Park, K, Park, P, Parker, J, Parsons, S, Pass, H, Pasternack, D, Pastore, A, Patch, A, Pauporte, I, Pea, A, Pearson, J, Pedamallu, C, Pederzoli, P, Peifer, M, Pennell, N, Perou, C, Petersen, G, Petrelli, N, Petryszak, R, Pfister, S, Phillips, M, Pich, O, Pickett, H, Pihl, T, Pillay, N, Pinder, S, Pinese, M, Pinho, A, Pitkanen, E, Pivot, X, Pineiro-Yanez, E, Planko, L, Plass, C, Polak, P, Pons, T, Popescu, I, Potapova, O, Prasad, A, Preston, S, Prinz, M, Pritchard, A, Prokopec, S, Provenzano, E, Puente, X, Puig, S, Pulido-Tamayo, S, Pupo, G, Purdie, C, Quinn, M, Rabionet, R, Rader, J, Radlwimmer, B, Radovic, P, Raeder, B, Ramakrishna, M, Ramakrishnan, K, Ramalingam, S, Raphael, B, Rathmell, W, Rausch, T, Reifenberger, G, Reimand, J, Reis-Filho, J, Reuter, V, Reyes-Salazar, I, Reyna, M, Riazalhosseini, Y, Richardson, A, Richter, J, Ringel, M, Ringner, M, Rino, Y, Rippe, K, Roach, J, Roberts, L, Roberts, N, Roberts, S, Robertson, A, Rodriguez, J, Rodriguez-Martin, B, Rodriguez-Gonzalez, F, Roehrl, M, Rohde, M, Rokutan, H, Romieu, G, Rooman, I, Roques, T, Rosebrock, D, Rosenberg, M, Rosenstiel, P, Rosenwald, A, Rowe, E, Rozen, S, Rubanova, Y, Rubin, M, Rubio-Perez, C, Rudneva, V, Rusev, B, Ruzzenente, A, Ratsch, G, Sabarinathan, R, Sabelnykova, V, Sadeghi, S, Saini, N, Saito-Adachi, M, Salcedo, A, Salgado, R, Salichos, L, Sallari, R, Saller, C, Salvia, R, Sam, M, Samra, J, Sanchez-Vega, F, Sander, C, Sanders, G, Sarin, R, Sasaki-Oku, A, Sauer, T, Sauter, G, Saw, R, Scardoni, M, Scarlett, C, Scarpa, A, Scelo, G, Schadendorf, D, Schein, J, Schilhabel, M, Schlomm, T, Schmidt, H, Schramm, S, Schreiber, S, Schultz, N, Schumacher, S, Schwarz, R, Scolyer, R, Scott, D, Scully, R, Seethala, R, Segre, A, Selander, I, Semple, C, Senbabaoglu, Y, Sengupta, S, Sereni, E, Serra, S, Sgroi, D, Shackleton, M, Shah, N, Shahabi, S, Shang, C, Shang, P, Shapira, O, Shelton, T, Shen, C, Shen, H, Shepherd, R, Shi, R, Shi, Y, Shiah, Y, Shibata, T, Shih, J, Shimizu, E, Shimizu, K, Shin, S, Shiraishi, Y, Shmaya, T, Shmulevich, I, Shorser, S, Short, C, Shrestha, R, Shringarpure, S, Shriver, C, Shuai, S, Sidiropoulos, N, Siebert, R, Sieuwerts, A, Sieverling, L, Signoretti, S, Sikora, K, Simbolo, M, Simon, R, Simons, J, Simpson, P, Singer, S, Sinnott-Armstrong, N, Sipahimalani, P, Skelly, T, Smid, M, Smith, J, Smith-McCune, K, Socci, N, Soloway, M, Song, L, Sood, A, Sothi, S, Sotiriou, C, Soulette, C, Span, P, Spellman, P, Sperandio, N, Spillane, A, Spiro, O, Spring, J, Staaf, J, Stadler, P, Staib, P, Stark, S, Stefansson, O, Stegle, O, Stein, L, Stenhouse, A, Stilgenbauer, S, Stratton, M, Stretch, J, Stunnenberg, H, Su, H, Su, X, Sun, R, Sungalee, S, Susak, H, Suzuki, A, Sweep, F, Szczepanowski, M, Sultmann, H, Yugawa, T, Tam, A, Tamborero, D, Tan, B, Tan, D, Tan, P, Tanaka, H, Taniguchi, H, Tanskanen, T, Tarabichi, M, Tarnuzzer, R, Tarpey, P, Taschuk, M, Tatsuno, K, Tavare, S, Taylor, D, Taylor-Weiner, A, Teh, B, Tembe, V, Temes, J, Thai, K, Thayer, S, Thiessen, N, Thomas, G, Thomas, S, Thompson, A, Thompson, J, Thompson, R, Thorne, H, Thorne, L, Thorogood, A, Tijanic, N, Timms, L, Tirabosco, R, Tojo, M, Tommasi, S, Toon, C, Toprak, U, Tortora, G, Tost, J, Totoki, Y, Townend, D, Traficante, N, Treilleux, I, Trotta, J, Trumper, L, Tsao, M, Tsunoda, T, Tubio, J, Tucker, O, Turkington, R, Turner, D, Tutt, A, Ueno, M, Ueno, N, Umbricht, C, Umer, H, Underwood, T, Urban, L, Urushidate, T, Ushiku, T, Uuskula-Reimand, L, Valencia, A, Van Den Berg, D, Van Laere, S, Van Loo, P, Van Meir, E, Van den Eynden, G, Van der Kwast, T, Vasudev, N, Vazquez, M, Vedururu, R, Veluvolu, U, Vembu, S, Verbeke, L, Vermeulen, P, Verrill, C, Viari, A, Vicente, D, Vicentini, C, Raghavan, K, Viksna, J, Vilain, R, Villasante, I, Vincent-Salomon, A, Visakorpi, T, Voet, D, Vyas, P, Vazquez-Garcia, I, Waddell, N, Wadelius, C, Wadi, L, Wagener, R, Wang, Q, Wang, Y, Wang, Z, Waring, P, Warnatz, H, Warrell, J, Warren, A, Wedge, D, Weichenhan, D, Weinberger, P, Weisenberger, D, Welch, I, Whalley, J, Whitaker, H, Wigle, D, Wilkerson, M, Williams, A, Wilmott, J, Wilson, G, Wilson, J, Wilson, R, Winterhoff, B, Wintersinger, J, Wiznerowicz, M, Wolf, S, Wong, B, Wong, T, Wong, W, Woo, Y, Wood, S, Wouters, B, Wright, A, Wright, D, Wright, M, Wu, C, Wu, D, Wu, G, Wu, J, Wu, K, Wu, Y, Xia, T, Xiang, Q, Xiao, X, Xing, R, Xiong, H, Xu, Q, Xu, Y, Yachida, S, Yamaguchi, R, Yamamoto, M, Yamamoto, S, Yamaue, H, Yang, F, Yang, H, Yang, J, Yang, L, Yang, S, Yang, T, Yang, Y, Yao, X, Yaspo, M, Yates, L, Yau, C, Ye, C, Yoon, C, Yoon, S, Yousif, F, Yu, J, Yu, K, Yu, W, Yu, Y, Yuan, K, Yuan, Y, Yuen, D, Zaikova, O, Zamora, J, Zapatka, M, Zenklusen, J, Zenz, T, Zeps, N, Zhang, C, Zhang, F, Zhang, H, Zhang, X, Zhang, Y, Zhang, Z, Zhao, Z, Zheng, L, Zheng, X, Zhou, W, Zhou, Y, Bin, Z, Zhu, H, Zhu, J, Zhu, S, Zou, L, Zou, X, Defazio, A, van As, N, van Deurzen, C, van de Vijver, M, van't Veer, L, von Mering, C, Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Tampere University, BioMediTech, TAYS Cancer Centre, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, University of St Andrews. Statistics, University of St Andrews. School of Medicine, University of Zurich, Gerstein, Mark B, Ding, Li, Bailey, Matthew H [0000-0003-4526-9727], Wheeler, David A [0000-0002-9056-6299], Gerstein, Mark B [0000-0002-9746-3719], Faculty of Economic and Social Sciences and Solvay Business School, Lauri Antti Aaltonen / Principal Investigator, Genome-Scale Biology (GSB) Research Program, Department of Medical and Clinical Genetics, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, Faculty of Medicine, and HUS Helsinki and Uusimaa Hospital District
Subjects: VARIANTS, 0302 clinical medicine, 706/648/697/129/2043, Databases, Genetic, Cancer genomics, SOMATIC POINT MUTATIONS, Càncer, lcsh:Science, Exome, Exome sequencing, Cancer, Base Composition, Neoplasms -- genetics, 1184 Genetics, developmental biology, physiology, 3100 General Physics and Astronomy, 3. Good health, 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Transformació genètica, Genetic databases, Erfðarannsóknir, Human, GENES, Science, 1600 General Chemistry, General Biochemistry, Genetics and Molecular Biology, RC0254, 03 medical and health sciences, Genetic, SDG 3 - Good Health and Well-being, 1300 General Biochemistry, Genetics and Molecular Biology, Exome Sequencing, Genetics, Humans, Author Correction, Retrospective Studies, Whole genome sequencing, Comparative genomics, Science & Technology, RC0254 Neoplasms. Tumors. Oncology (including Cancer), INSERTIONS, DNA, PERFORMANCE, Human genetics, Communication and replication, Cancérologie, 692/4028/67/69, Genòmica, 030104 developmental biology, Mutation, Genome mutation, Human genome, lcsh:Q, COMPREHENSIVE CHARACTERIZATION, Genètica, 0301 basic medicine, Medizin, General Physics and Astronomy, Genome, Whole Exome Sequencing, Genetic transformation, International Cancer Genome Consortium, Neoplasms, 631/114/2399, Genamengi, Medicine and Health Sciences, Medicine(all), Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Multidisciplinary, 318 Medical biotechnology, Exome -- genetics, article, Exons, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Multidisciplinary Sciences, CAPTURE, 1181 Ecology, evolutionary biology, oncology, DNA, Intergenic, 139, Medical Genetics, Biotechnology, ICGC/TCGA Pan-Cancer Analysis, 3122 Cancers, 610 Medicine & health, 45/23, QH426 Genetics, Biology, MC3 Working Group, Databases, Germline mutation, PCAWG novel somatic mutation calling methods working group, Krabbameinsrannsóknir, Cancer Genome Atlas, Genome, Human -- genetics, ddc:610, QH426, Medicinsk genetik, Krabbamein, Intergenic, Whole Genome Sequencing, Genome, Human, Human Genome, PCAWG Consortium, DAS, General Chemistry, DELETIONS, Good Health and Well Being, 10032 Clinic for Oncology and Hematology, 3111 Biomedicine, 631/1647/2217/748
Abstract: MC3 Working Group: Rehan Akbani21, Pavana Anur22, Matthew H. Bailey1,2,3, Alex Buchanan9, Kami Chiotti9, Kyle Covington12,23, Allison Creason9, Li Ding1,2,3,20, Kyle Ellrott9, Yu Fan21, Steven Foltz1,2, Gad Getz8,14,15,16, Walker Hale12, David Haussler24,25, Julian M. Hess8,26, Carolyn M. Hutter27, Cyriac Kandoth28, Katayoon Kasaian29,30, Melpomeni Kasapi27, Dave Larson1 , Ignaty Leshchiner8, John Letaw31, Singer Ma32, Michael D. McLellan1,3,20, Yifei Men32, Gordon B. Mills33,34, Beifang Niu35, Myron Peto22, Amie Radenbaugh24, Sheila M. Reynolds36, Gordon Saksena8, Heidi Sofia27, Chip Stewart8, Adam J. Struck31, Joshua M. Stuart24,37, Wenyi Wang21, John N. Weinstein38, David A. Wheeler12,13, Christopher K. Wong24,39, Liu Xi12 & Kai Ye40,41 21Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 22Molecular and Medical Genetics, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 23Castle Biosciences Inc, Friendswood, TX 77546, USA. 24UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 25Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 26Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02114, USA. 27National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20894, USA. 28Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. 29Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. 30Canada’s Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4S6, Canada. 31Computational Biology Program, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA. 32DNAnexus Inc, Mountain View, CA 94040, USA. 33Department of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA. 34Precision Oncology, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 35Computer Network Information Center, Chinese Academy of Sciences, Beijing, China. 36Institute for Systems Biology, Seattle, WA 98109, USA. 37Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 38Department of Bioinformatics and Computational Biology and Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 39Biomolecular Engineering Department, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 40School of Elect, PCAWG novel somatic mutation calling methods working group: Matthew H. Bailey1,2,3, Beifang Niu35, Matthias Bieg42,43, Paul C. Boutros6,44,45,46, Ivo Buchhalter43,47,48, Adam P. Butler49, Ken Chen50, Zechen Chong51, Li Ding1,2,3,20, Oliver Drechsel52,53, Lewis Jonathan Dursi6,7, Roland Eils47,48,54,55, Kyle Ellrott9, Shadrielle M. G. Espiritu6, Yu Fan21, Robert S. Fulton1,3,20, Shengjie Gao56, Josep L. l. Gelpi57,58, Mark B. Gerstein5,18,19, Gad Getz8,14,15,16, Santiago Gonzalez59,60, Ivo G. Gut52,61, Faraz Hach62,63, Michael C. Heinold47,48, Julian M. Hess8,26, Jonathan Hinton49, Taobo Hu64, Vincent Huang6, Yi Huang65,66, Barbara Hutter43,67,68, David R. Jones49, Jongsun Jung69, Natalie Jäger47, Hyung-Lae Kim70, Kortine Kleinheinz47,48, Sushant Kumar5,19, Yogesh Kumar64, Christopher M. Lalansingh6, Ignaty Leshchiner8, Ivica Letunic71, Dimitri Livitz8, Eric Z. Ma64, Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Michael D. McLellan1,3,20, Andrew Menzies49, Ana Milovanovic57, Morten Muhlig Nielsen73, Stephan Ossowski52,53,74, Nagarajan Paramasivam43,47, Jakob Skou Pedersen73,75, Marc D. Perry76,77, Montserrat Puiggròs57, Keiran M. Raine49, Esther Rheinbay8,14,72, Romina Royo57, S. Cenk Sahinalp62,78,79, Gordon Saksena8, Iman Sarrafi62,78, Matthias Schlesner47,80, Jared T. Simpson6,17, Lucy Stebbings49, Chip Stewart8, Miranda D. Stobbe52,61, Jon W. Teague49, Grace Tiao8, David Torrents57,81, Jeremiah A. Wala8,14,82, Jiayin Wang1,40,66, Wenyi Wang21, Sebastian M. Waszak60, Joachim Weischenfeldt60,83,84, Michael C. Wendl1,10,11, Johannes Werner47,85, Zhenggang Wu64, Hong Xue64, Sergei Yakneen60, Takafumi N. Yamaguchi6, Kai Ye40,41, Venkata D. Yellapantula20,86, Christina K. Yung76 & Junjun Zhang76, PCAWG Consortium: Lauri A. Aaltonen87, Federico Abascal49, Adam Abeshouse88, Hiroyuki Aburatani89, David J. Adams49, Nishant Agrawal90, Keun Soo Ahn91, Sung-Min Ahn92, Hiroshi Aikata93, Rehan Akbani21, Kadir C. Akdemir50, Hikmat Al-Ahmadie88, Sultan T. Al-Sedairy94, Fatima Al-Shahrour95, Malik Alawi96,97, Monique Albert98, Kenneth Aldape99,100, Ludmil B. Alexandrov49,101,102, Adrian Ally30, Kathryn Alsop103, Eva G. Alvarez104,105,106, Fernanda Amary107, Samirkumar B. Amin108,109,110, Brice Aminou76, Ole Ammerpohl111,112, Matthew J. Anderson113, Yeng Ang114, Davide Antonello115, Pavana Anur22, Samuel Aparicio116, Elizabeth L. Appelbaum1,117, Yasuhito Arai118, Axel Aretz119, Koji Arihiro93, Shun-ichi Ariizumi120, Joshua Armenia121, Laurent Arnould122, Sylvia Asa123,124, Yassen Assenov125, Gurnit Atwal6,126,127, Sietse Aukema112,128, J. Todd Auman129, Miriam R. Aure130, Philip Awadalla6,126, Marta Aymerich131, Gary D. Bader126, Adrian Baez-Ortega132, Matthew H. Bailey1,2,3, Peter J. Bailey133, Miruna Balasundaram30, Saianand Balu134, Pratiti Bandopadhayay8,135,136, Rosamonde E. Banks137, Stefano Barbi138, Andrew P. Barbour139,140, Jonathan Barenboim6, Jill Barnholtz-Sloan141,142, Hugh Barr143, Elisabet Barrera59, John Bartlett98,144, Javier Bartolome57, Claudio Bassi115, Oliver F. Bathe145,146, Daniel Baumhoer147, Prashant Bavi148, Stephen B. Baylin149,150, Wojciech Bazant59, Duncan Beardsmore151, Timothy A. Beck152,153, Sam Behjati49, Andreas Behren154, Beifang Niu35, Cindy Bell155, Sergi Beltran52,61, Christopher Benz156, Andrew Berchuck157, Anke K. Bergmann158, Erik N. Bergstrom101,102, Benjamin P. Berman159,160,161, Daniel M. Berney162, Stephan H. Bernhart163,164,165, Rameen Beroukhim8,14,82, Mario Berrios166, Samantha Bersani167, Johanna Bertl73,168, Miguel Betancourt169, Vinayak Bhandari6,44, Shriram G. Bhosle49, Andrew V. Biankin133,170,171,172, Matthias Bieg42,43, Darell Bigner173, Hans Binder163,164, Ewan Birney59, Michael Birrer72, Nidhan K. Biswas174, Bodil Bjerkehagen147,175, Tom Bodenheimer134, Lori Boice176, Giada Bonizzato177, Johann S. De Bono178, Arnoud Boot179,180, Moiz S. Bootwalla166, Ake Borg181, Arndt Borkhardt182, Keith A. Boroevich183,184, Ivan Borozan6, Christoph Borst185, Marcus Bosenberg186, Mattia Bosio52,53,57, Jacqueline Boultwood187, Guillaume Bourque188,189, Paul C. Boutros6,44,45,46, G. Steven Bova190, David T. Bowen49,191, Reanne Bowlby30, David D. L. Bowtell103, Sandrine Boyault192, Rich Boyce59, Jeffrey Boyd193, Alvis Brazma59, Paul Brennan194, Daniel S. Brewer195,196, Arie B. Brinkman197, Robert G. Bristow44,198,199,200,201, Russell R. Broaddus99, Jane E. Brock202, Malcolm Brock203, Annegien Broeks204, Angela N. Brooks8,24,37,82, Denise Brooks30, Benedikt Brors67,205,206, Søren Brunak207,208, Timothy J. C. Bruxner113,209, Alicia L. Bruzos104,105,106, Alex Buchanan9, Ivo Buchhalter43,47,48, Christiane Buchholz210, Susan Bullman8,82, Hazel Burke211, Birgit Burkhardt212, Kathleen H. Burns213,214, John Busanovich8,215, Carlos D. Bustamante216,217, Adam P. Butler49, Atul J. Butte218, Niall J. Byrne76, Anne-Lise Børresen-Dale130,219, Samantha J. Caesar-Johnson220, Andy Cafferkey59, Declan Cahill221, Claudia Calabrese59,60, Carlos Caldas222,223, Fabien Calvo224, Niedzica Camacho178, Peter J. Campbell49,225, Elias Campo226,227, Cinzia Cantù177, Shaolong Cao21, Thomas E. Carey228, Joana Carlevaro-Fita229,230,231, Rebecca Carlsen30, Ivana Cataldo167,177, Mario Cazzola232, Jonathan Cebon154, Robert Cerfolio233, Dianne E. Chadwick234, Dimple Chakravarty235, Don Chalmers236, Calvin Wing Yiu Chan47,237, Kin Chan238, Michelle Chan-Seng-Yue148, Vishal S. Chandan239, David K. Chang133,170, Stephen J. Chanock240, Lorraine A. Chantrill170,241, Aurélien Chateigner76,242, Nilanjan Chatterjee149,243, Kazuaki Chayama93, Hsiao-Wei Chen114,121, Jieming Chen218, Ken Chen50, Yiwen Chen21, Zhaohong Chen244, Andrew D. Cherniack8,82, Jeremy Chien245, Yoke-Eng Chiew246,247, Suet-Feung Chin222,223, Juok Cho8, Sunghoon Cho248, Jung Kyoon Choi249, Wan Choi250, Christine Chomienne251, Zechen Chong51, Su Pin Choo252, Angela Chou170,246, Angelika N. Christ113, Elizabeth L. Christie103, Eric Chuah30, Carrie Cibulskis8, Kristian Cibulskis8, Sara Cingarlini253, Peter Clapham49, Alexander Claviez254, Sean Cleary148,255, Nicole Cloonan256, Marek Cmero257,258,259, Colin C. Collins62, Ashton A. Connor255,260, Susanna L. Cooke133, Colin S. Cooper178,196,261, Leslie Cope149, Vincenzo Corbo138,177, Matthew G. Cordes1,262, Stephen M. Cordner263, Isidro Cortés-Ciriano264,265,266, Kyle Covington12,23, Prue A. Cowin267, Brian Craft24, David Craft8,268, Chad J. Creighton269, Yupeng Cun270, Erin Curley271, Ioana Cutcutache179,180, Karolina Czajka272, Bogdan Czerniak99,273, Rebecca A. Dagg274, Ludmila Danilova149, Maria Vittoria Davi275, Natalie R. Davidson276,277,278,279,280, Helen Davies49,281,282, Ian J. Davis283, Brandi N. Davis-Dusenbery284, Kevin J. Dawson49, Francisco M. De La Vega216,217,285, Ricardo De Paoli-Iseppi211, Timothy Defreitas8, Angelo P. Dei Tos286, Olivier Delaneau287,288,289, John A. Demchok220, Jonas Demeulemeester290,291, German M. Demidov52,53,74, Deniz Demircioğlu292,293, Nening M. Dennis221, Robert E. Denroche148, Stefan C. Dentro49,290,294, Nikita Desai76, Vikram Deshpande72, Amit G. Deshwar295, Christine Desmedt296,297, Jordi Deu-Pons298,299, Noreen Dhalla30, Neesha C. Dhani300, Priyanka Dhingra301,302, Rajiv Dhir303, Anthony DiBiase304, Klev Diamanti305, Li Ding1,2,3,20, Shuai Ding306, Huy Q. Dinh159, Luc Dirix307, HarshaVardhan Doddapaneni12, Nilgun Donmez62,78, Michelle T. Dow244, Ronny Drapkin308, Oliver Drechsel52,53, Ruben M. Drews223, Serge Serge49, Tim Dudderidge150,221, Ana Dueso-Barroso57, Andrew J. Dunford8, Michael Dunn309, Lewis Jonathan Dursi6,7, Fraser R. Duthie133,310, Ken Dutton-Regester311, Jenna Eagles272, Douglas F. Easton312,313, Stuart Edmonds314, Paul A. Edwards223,315, Sandra E. Edwards178, Rosalind A. Eeles178,221, Anna Ehinger316, Juergen Eils54,55, Roland Eils47,48,54,55, Adel El-Naggar99,273, Matthew Eldridge223, Kyle Ellrott9, Serap Erkek60, Georgia Escaramis53,317,318, Shadrielle M. G. Espiritu6, Xavier Estivill53,319, Dariush Etemadmoghadam103, Jorunn E. Eyfjord320, Bishoy M. Faltas280, Daiming Fan321, Yu Fan21, William C. Faquin72, Claudiu Farcas244, Matteo Fassan322, Aquila Fatima323, Francesco Favero324, Nodirjon Fayzullaev76, Ina Felau220, Sian Fereday103, Martin L. Ferguson325, Vincent Ferretti76,326, Lars Feuerbach205, Matthew A. Field327, J. Lynn Fink57,113, Gaetano Finocchiaro328, Cyril Fisher221, Matthew W. Fittall290, Anna Fitzgerald329, Rebecca C. Fitzgerald282, Adrienne M. Flanagan330, Neil E. Fleshner331, Paul Flicek59, John A. Foekens332, Kwun M. Fong333, Nuno A. Fonseca59,334, Christopher S. Foster335,336, Natalie S. Fox6, Michael Fraser6, Scott Frazer8, Milana Frenkel-Morgenstern337, William Friedman338, Joan Frigola298, Catrina C. Fronick1,262, Akihiro Fujimoto184, Masashi Fujita184, Masashi Fukayama339, Lucinda A. Fulton1 , Robert S. Fulton1,3,20, Mayuko Furuta184, P. Andrew Futreal340, Anja Füllgrabe59, Stacey B. Gabriel8, Steven Gallinger148,255,260, Carlo Gambacorti-Passerini341, Jianjiong Gao121, Shengjie Gao56, Levi Garraway82, Øystein Garred342, Erik Garrison49, Dale W. Garsed103, Nils Gehlenborg8,343, Josep L. l. Gelpi57,58, Joshy George110, Daniela S. Gerhard344, Clarissa Gerhauser345, Jeffrey E. Gershenwald346,347, Mark B. Gerstein5,18,19, Moritz Gerstung59,60, Gad Getz8,14,15,16, Mohammed Ghori49, Ronald Ghossein348, Nasra H. Giama349, Richard A. Gibbs12, Anthony J. Gill170,350, Pelvender Gill351, Dilip D. Giri348, Dominik Glodzik49, Vincent J. Gnanapragasam352,353, Maria Elisabeth Goebler354, Mary J. Goldman24, Carmen Gomez355, Santiago Gonzalez59,60, Abel Gonzalez-Perez298,299,356, Dmitry A. Gordenin357, James Gossage358, Kunihito Gotoh359, Ramaswamy Govindan3, Dorthe Grabau360, Janet S. Graham133,361, Robert C. Grant148,260, Anthony R. Green315, Eric Green27, Liliana Greger59, Nicola Grehan282, Sonia Grimaldi177, Sean M. Grimmond362, Robert L. Grossman363, Adam Grundhoff97,364, Gunes Gundem88, Qianyun Guo75, Manaswi Gupta8, Shailja Gupta365, Ivo G. Gut52,61, Marta Gut52,61, Jonathan Göke292,366, Gavin Ha8, Andrea Haake111, David Haan37, Siegfried Haas185, Kerstin Haase290, James E. Haber367, Nina Habermann60, Faraz Hach62,63, Syed Haider6, Natsuko Hama118, Freddie C. Hamdy351, Anne Hamilton267, Mark P. Hamilton368, Leng Han369, George B. Hanna370, Martin Hansmann371, Nicholas J. Haradhvala8,72, Olivier Harismendy102,372, Ivon Harliwong113, Arif O. Harmanci5,373, Eoghan Harrington374, Takanori Hasegawa375, David Haussler24,25, Steve Hawkins223, Shinya Hayami376, Shuto Hayashi375, D. Neil Hayes134,377,378, Stephen J. Hayes379,380, Nicholas K. Hayward211,311, Steven Hazell221, Yao He381, Allison P. Heath382, Simon C. Heath52,61, David Hedley300, Apurva M. Hegde38, David I. Heiman8, Michael C. Heinold47,48, Zachary Heins88, Lawrence E. Heisler152, Eva Hellstrom-Lindberg383, Mohamed Helmy384, Seong Gu Heo385, Austin J. Hepperla134, José María Heredia-Genestar386, Carl Herrmann47,48,387, Peter Hersey211, Julian M. Hess8,26, Holmfridur Hilmarsdottir320, Jonathan Hinton49, Satoshi Hirano388, Nobuyoshi Hiraoka389, Katherine A. Hoadley134,390, Asger Hobolth75,168, Ermin Hodzic78, Jessica I. Hoell182, Steve Hoffmann163,164,165,391, Oliver Hofmann392, Andrea Holbrook166, Aliaksei Z. Holik53, Michael A. Hollingsworth393, Oliver Holmes209,311, Robert A. Holt30, Chen Hong205,237, Eun Pyo Hong385, Jongwhi H. Hong394, Gerrit K. Hooijer395, Henrik Hornshøj73, Fumie Hosoda118, Yong Hou56,396, Volker Hovestadt397, William Howat352, Alan P. Hoyle134, Ralph H. Hruban149, Jianhong Hu12, Taobo Hu64, Xing Hua240, Kuan-lin Huang1,398, Mei Huang176, Mi Ni Huang179,180, Vincent Huang6, Yi Huang65,66, Wolfgang Huber60, Thomas J. Hudson272,399, Michael Hummel400, Jillian A. Hung246,247, David Huntsman401, Ted R. Hupp402, Jason Huse88, Matthew R. Huska403, Barbara Hutter43,67,68, Carolyn M. Hutter27, Daniel Hübschmann48,54,404,405,406, Christine A. Iacobuzio-Donahue348, Charles David Imbusch205, Marcin Imielinski407,408, Seiya Imoto375, William B. Isaacs409, Keren Isaev6,44, Shumpei Ishikawa410, Murat Iskar397, S. M. Ashiqul Islam244, Michael Ittmann411,412,413, Sinisa Ivkovic284, Jose M. G. Izarzugaza414, Jocelyne Jacquemier415, Valerie Jakrot211, Nigel B. Jamieson133,172,416, Gun Ho Jang148, Se Jin Jang417, Joy C. Jayaseelan12, Reyka Jayasinghe1 , Stuart R. Jefferys134, Karine Jegalian418, Jennifer L. Jennings419, Seung-Hyup Jeon250, Lara Jerman60,420, Yuan Ji421,422, Wei Jiao6, Peter A. Johansson311, Amber L. Johns170, Jeremy Johns272, Rory Johnson230,423, Todd A. Johnson183, Clemency Jolly290, Yann Joly424, Jon G. Jonasson320, Corbin D. Jones425, David R. Jones49, David T. W. Jones426,427, Nic Jones428, Steven J. M. Jones30, Jos Jonkers204, Young Seok Ju49,249, Hartmut Juhl429, Jongsun Jung69, Malene Juul73, Randi Istrup Juul73, Sissel Juul374, Natalie Jäger47, Rolf Kabbe47, Andre Kahles276,277,278,279,430, Abdullah Kahraman431,432,433, Vera B. Kaiser434, Hojabr Kakavand211, Sangeetha Kalimuthu148, Christof von Kalle405, Koo Jeong Kang91, Katalin Karaszi351, Beth Karlan435, Rosa Karlić436, Dennis Karsch437, Katayoon Kasaian29,30, Karin S. Kassahn113,438, Hitoshi Katai439, Mamoru Kato440, Hiroto Katoh410, Yoshiiku Kawakami93, Jonathan D. Kay117, Stephen H. Kazakoff209,311, Marat D. Kazanov441,442,443, Maria Keays59, Electron Kebebew444,445, Richard F. Kefford446, Manolis Kellis8,447, James G. Kench170,350,448, Catherine J. Kennedy246,247, Jules N. A. Kerssemakers47, David Khoo273, Vincent Khoo221, Narong Khuntikeo115,449, Ekta Khurana301,302,450,451, Helena Kilpinen117, Hark Kyun Kim452, Hyung-Lae Kim70, Hyung-Yong Kim415, Hyunghwan Kim250, Jaegil Kim8, Jihoon Kim453, Jong K. Kim454, Youngwook Kim455,456, Tari A. King457,458,459, Wolfram Klapper128, Kortine Kleinheinz47,48, Leszek J. Klimczak460, Stian Knappskog49,461, Michael Kneba437, Bartha M. Knoppers424, Youngil Koh462,463, Jan Komorowski305,464, Daisuke Komura410, Mitsuhiro Komura375, Gu Kong415, Marcel Kool426,465, Jan O. Korbel59,60, Viktoriya Korchina12, Andrey Korshunov465, Michael Koscher465, Roelof Koster466, Zsofia Kote-Jarai178, Antonios Koures244, Milena Kovacevic284, Barbara Kremeyer49, Helene Kretzmer164,165, Markus Kreuz467, Savitri Krishnamurthy99,468, Dieter Kube469, Kiran Kumar8, Pardeep Kumar221, Sushant Kumar5,19, Yogesh Kumar64, Ritika Kundra114,121, Kirsten Kübler8,14,72, Ralf Küppers470, Jesper Lagergren383,471, Phillip H. Lai166, Peter W. Laird472, Sunil R. Lakhani473, Christopher M. Lalansingh6, Emilie Lalonde6, Fabien C. Lamaze6, Adam Lambert351, Eric Lander8, Pablo Landgraf474,475, Luca Landoni115, Anita Langerød130, Andrés Lanzós230,231,423, Denis Larsimont476, Erik Larsson477, Mark Lathrop189, Loretta M. S. Lau478, Chris Lawerenz55, Rita T. Lawlor177, Michael S. Lawrence8,72,183, Alexander J. Lazar99,108, Xuan Le479, Darlene Lee30, Donghoon Lee5, Eunjung Alice Lee480, Hee Jin Lee417, Jake June-Koo Lee264,266, Jeong-Yeon Lee481, Juhee Lee482, Ming Ta Michael Lee340, Henry Lee-Six49, Kjong-Van Lehmann276,277,278,279,430, Hans Lehrach483, Dido Lenze400, Conrad R. Leonard209,311, Daniel A. Leongamornlert49,178, Ignaty Leshchiner8, Louis Letourneau484, Ivica Letunic71, Douglas A. Levine88,485, Lora Lewis12, Tim Ley486, Chang Li56,396, Constance H. Li6,44, Haiyan Irene Li30, Jun Li21, Lin Li56, Shantao Li5, Siliang Li56,396, Xiaobo Li56,396, Xiaotong Li5, Xinyue Li56, Yilong Li49, Han Liang21, Sheng-Ben Liang234, Peter Lichter68,397, Pei Lin8, Ziao Lin8,487, W. M. Linehan488, Ole Christian Lingjærde489, Dongbing Liu56,396, Eric Minwei Liu88,301,302, Fei-Fei Liu201,490, Fenglin Liu381,491, Jia Liu492, Xingmin Liu56,396, Julie Livingstone6, Dimitri Livitz8, Naomi Livni221, Lucas Lochovsky5,19,110, Markus Loeffler467, Georgina V. Long211, Armando Lopez-Guillermo493, Shaoke Lou5,19, David N. Louis72, Laurence B. Lovat117, Yiling Lu38, Yong-Jie Lu162,494, Youyong Lu495,496,497, Claudio Luchini167, Ilinca Lungu144,148, Xuemei Luo152, Hayley J. Luxton117, Andy G. Lynch223,315,498, Lisa Lype36, Cristina López111,112, Carlos López-Otín499, Eric Z. Ma64, Yussanne Ma30, Gaetan MacGrogan500, Shona MacRae501, Geoff Macintyre223, Tobias Madsen73, Kazuhiro Maejima184, Andrea Mafficini177, Dennis T. Maglinte166,502, Arindam Maitra174, Partha P. Majumder174, Luca Malcovati232, Salem Malikic62,78, Giuseppe Malleo115, Graham J. Mann211,246,503, Luisa Mantovani-Löffler504, Kathleen Marchal505,506, Giovanni Marchegiani115, Elaine R. Mardis1,193,507, Adam A. Margolin31, Maximillian G. Marin37, Florian Markowetz223,315, Julia Markowski403, Jeffrey Marks508, Tomas Marques-Bonet61,81,386,509, Marco A. Marra30, Luke Marsden351, John W. M. Martens332, Sancha Martin49,510, Jose I. Martin-Subero81,511, Iñigo Martincorena49, Alexander Martinez-Fundichely301,302,451 Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Charlie E. Massie223, Thomas J. Matthew37, Lucy Matthews178, Erik Mayer221,512, Simon Mayes513, Michael Mayo30, Faridah Mbabaali272, Karen McCune514, Ultan McDermott49, Patrick D. McGillivray19, Michael D. McLellan1,3,20, John D. McPherson148,272,515, John R. McPherson179,180, Treasa A. McPherson260, Samuel R. Meier8, Alice Meng516, Shaowu Meng134, Andrew Menzies49, Neil D. Merrett115,517, Sue Merson178, Matthew Meyerson8,14,82, William U. Meyerson4,5, Piotr A. Mieczkowski518, George L. Mihaiescu76, Sanja Mijalkovic284, Ana Mijalkovic Mijalkovic-Lazic284, Tom Mikkelsen519, Michele Milella253, Linda Mileshkin103, Christopher A. Miller1 , David K. Miller113,170, Jessica K. Miller272, Gordon B. Mills33,34, Ana Milovanovic57, Sarah Minner520, Marco Miotto115, Gisela Mir Arnau267, Lisa Mirabello240, Chris Mitchell103, Thomas J. Mitchell49,315,352, Satoru Miyano375, Naoki Miyoshi375, Shinichi Mizuno521, Fruzsina Molnár-Gábor522, Malcolm J. Moore300, Richard A. Moore30, Sandro Morganella49, Quaid D. Morris127,490, Carl Morrison523,524, Lisle E. Mose134, Catherine D. Moser349, Ferran Muiños298,299, Loris Mularoni298,299, Andrew J. Mungall30, Karen Mungall30, Elizabeth A. Musgrove133, Ville Mustonen525,526,527, David Mutch528, Francesc Muyas52,53,74, Donna M. Muzny12, Alfonso Muñoz59, Jerome Myers529, Ola Myklebost461, Peter Möller530, Genta Nagae89, Adnan M. Nagrial170, Hardeep K. Nahal-Bose76, Hitoshi Nakagama531, Hidewaki Nakagawa184, Hiromi Nakamura118, Toru Nakamura388, Kaoru Nakano184, Tannistha Nandi532, Jyoti Nangalia49, Mia Nastic284, Arcadi Navarro61,81,386, Fabio C. P. Navarro19, David E. Neal223,352, Gerd Nettekoven533, Felicity Newell209,311, Steven J. Newhouse59, Yulia Newton37, Alvin Wei Tian Ng534, Anthony Ng535, Jonathan Nicholson49, David Nicol221, Yongzhan Nie321,536, G. Petur Nielsen72, Morten Muhlig Nielsen73, Serena Nik-Zainal49,281,282,537, Michael S. Noble8, Katia Nones209,311, Paul A. Northcott538, Faiyaz Notta148,539, Brian D. O’Connor76,540, Peter O’Donnell541, Maria O’Donovan282, Sarah O’Meara49, Brian Patrick O’Neill542, J. Robert O’Neill543, David Ocana59, Angelica Ochoa88, Layla Oesper544, Christopher Ogden221, Hideki Ohdan93, Kazuhiro Ohi375, Lucila Ohno-Machado244, Karin A. Oien523,545, Akinyemi I. Ojesina546,547,548, Hidenori Ojima549, Takuji Okusaka550, Larsson Omberg551, Choon Kiat Ong552, Stephan Ossowski52,53,74, German Ott553, B. F. Francis Ouellette76,554, Christine P’ng6, Marta Paczkowska6, Salvatore Paiella115, Chawalit Pairojkul523, Marina Pajic170, Qiang Pan-Hammarström56,555, Elli Papaemmanuil49, Irene Papatheodorou59, Nagarajan Paramasivam43,47, Ji Wan Park385, Joong-Won Park556, Keunchil Park557,558, Kiejung Park559, Peter J. Park264,266, Joel S. Parker518, Simon L. Parsons124, Harvey Pass560, Danielle Pasternack272, Alessandro Pastore276, Ann-Marie Patch209,311, Iris Pauporté251, Antonio Pea115, John V. Pearson209,311, Chandra Sekhar Pedamallu8,14,82, Jakob Skou Pedersen73,75, Paolo Pederzoli115, Martin Peifer270, Nathan A. Pennell561, Charles M. Perou129,518, Marc D. Perry76,77, Gloria M. Petersen562, Myron Peto22, Nicholas Petrelli563, Robert Petryszak59, Stefan M. Pfister426,465,564, Mark Phillips424, Oriol Pich298,299, Hilda A. Pickett478, Todd D. Pihl565, Nischalan Pillay566, Sarah Pinder567, Mark Pinese170, Andreia V. Pinho568, Esa Pitkänen60, Xavier Pivot569, Elena Piñeiro-Yáñez95, Laura Planko533, Christoph Plass345, Paz Polak8,14,15, Tirso Pons570, Irinel Popescu571, Olga Potapova572, Aparna Prasad52, Shaun R. Preston573, Manuel Prinz47, Antonia L. Pritchard311, Stephenie D. Prokopec6, Elena Provenzano574, Xose S. Puente499, Sonia Puig176, Montserrat Puiggròs57, Sergio Pulido-Tamayo505,506, Gulietta M. Pupo246, Colin A. Purdie575, Michael C. Quinn209,311, Raquel Rabionet52,53,576, Janet S. Rader577, Bernhard Radlwimmer397, Petar Radovic284, Benjamin Raeder60, Keiran M. Raine49, Manasa Ramakrishna49, Kamna Ramakrishnan49, Suresh Ramalingam578, Benjamin J. Raphael579, W. Kimryn Rathmell580, Tobias Rausch60, Guido Reifenberger475, Jüri Reimand6,44, Jorge Reis-Filho348, Victor Reuter348, Iker Reyes-Salazar298, Matthew A. Reyna579, Sheila M. Reynolds36, Esther Rheinbay8,14,72, Yasser Riazalhosseini189, Andrea L. Richardson323, Julia Richter111,128, Matthew Ringel581, Markus Ringnér181, Yasushi Rino582, Karsten Rippe405, Jeffrey Roach583, Lewis R. Roberts349, Nicola D. Roberts49, Steven A. Roberts584, A. Gordon Robertson30, Alan J. Robertson113, Javier Bartolomé Rodriguez57, Bernardo Rodriguez-Martin104,105,106, F. Germán Rodríguez-González83,332, Michael H. A. Roehrl44,123,148,234,585,586, Marius Rohde587, Hirofumi Rokutan440, Gilles Romieu588, Ilse Rooman170, Tom Roques262, Daniel Rosebrock8, Mara Rosenberg8,72, Philip C. Rosenstiel589, Andreas Rosenwald590, Edward W. Rowe221,591, Romina Royo57, Steven G. Rozen179,180,592, Yulia Rubanova17,127, Mark A. Rubin423,593,594,595,596, Carlota Rubio-Perez298,299,597, Vasilisa A. Rudneva60, Borislav C. Rusev177, Andrea Ruzzenente598, Gunnar Rätsch276,277,278,279,280,430, Radhakrishnan Sabarinathan298,299,599, Veronica Y. Sabelnykova6, Sara Sadeghi30, S. Cenk Sahinalp62,78,79, Natalie Saini357, Mihoko Saito-Adachi440, Gordon Saksena8, Adriana Salcedo6, Roberto Salgado600, Leonidas Salichos5,19, Richard Sallari8, Charles Saller601, Roberto Salvia115, Michelle Sam272, Jaswinder S. Samra115,602, Francisco Sanchez-Vega114,121, Chris Sander276,603,604, Grant Sanders134, Rajiv Sarin605, Iman Sarrafi62,78, Aya Sasaki-Oku184, Torill Sauer489, Guido Sauter520, Robyn P. M. Saw211, Maria Scardoni167, Christopher J. Scarlett170,606, Aldo Scarpa177, Ghislaine Scelo194, Dirk Schadendorf68,607, Jacqueline E. Schein30, Markus B. Schilhabel589, Matthias Schlesner47,80, Thorsten Schlomm84,608, Heather K. Schmidt1 , Sarah-Jane Schramm246, Stefan Schreiber609, Nikolaus Schultz121, Steven E. Schumacher8,323, Roland F. Schwarz59,403,405,610, Richard A. Scolyer211,448,602, David Scott428, Ralph Scully611, Raja Seethala612, Ayellet V. Segre8,613, Iris Selander260, Colin A. Semple434, Yasin Senbabaoglu276, Subhajit Sengupta614, Elisabetta Sereni115, Stefano Serra585, Dennis C. Sgroi72, Mark Shackleton103, Nimish C. Shah352, Sagedeh Shahabi234, Catherine A. Shang329, Ping Shang211, Ofer Shapira8,323, Troy Shelton271, Ciyue Shen603,604, Hui Shen615, Rebecca Shepherd49, Ruian Shi490, Yan Shi134, Yu-Jia Shiah6, Tatsuhiro Shibata118,616, Juliann Shih8,82, Eigo Shimizu375, Kiyo Shimizu617, Seung Jun Shin618, Yuichi Shiraishi375, Tal Shmaya285, Ilya Shmulevich36, Solomon I. Shorser6, Charles Short59, Raunak Shrestha62, Suyash S. Shringarpure217, Craig Shriver619, Shimin Shuai6,126, Nikos Sidiropoulos83, Reiner Siebert112,620, Anieta M. Sieuwerts332, Lina Sieverling205,237, Sabina Signoretti202,621, Katarzyna O. Sikora177, Michele Simbolo138, Ronald Simon520, Janae V. Simons134, Jared T. Simpson6,17, Peter T. Simpson473, Samuel Singer115,458, Nasa Sinnott-Armstrong8,217, Payal Sipahimalani30, Tara J. Skelly390, Marcel Smid332, Jaclyn Smith622, Karen Smith-McCune514, Nicholas D. Socci276, Heidi J. Sofia27, Matthew G. Soloway134, Lei Song240, Anil K. Sood623,624,625, Sharmila Sothi626, Christos Sotiriou244, Cameron M. Soulette37, Paul N. Span627, Paul T. Spellman22, Nicola Sperandio177, Andrew J. Spillane211, Oliver Spiro8, Jonathan Spring628, Johan Staaf181, Peter F. Stadler163,164,165, Peter Staib629, Stefan G. Stark277,279,618,630, Lucy Stebbings49, Ólafur Andri Stefánsson631, Oliver Stegle59,60,632, Lincoln D. Stein6,126, Alasdair Stenhouse633, Chip Stewart8, Stephan Stilgenbauer634, Miranda D. Stobbe52,61, Michael R. Stratton49, Jonathan R. Stretch211, Adam J. Struck31, Joshua M. Stuart24,37, Henk G. Stunnenberg396,635, Hong Su56,396, Xiaoping Su99, Ren X. Sun6, Stephanie Sungalee60, Hana Susak52,53, Akihiro Suzuki89,636, Fred Sweep637, Monika Szczepanowski128, Holger Sültmann67,638, Takashi Yugawa617, Angela Tam30, David Tamborero298,299, Benita Kiat Tee Tan639, Donghui Tan518, Patrick Tan180,532,592,640, Hiroko Tanaka375, Hirokazu Taniguchi616, Tomas J. Tanskanen641, Maxime Tarabichi49,290, Roy Tarnuzzer220, Patrick Tarpey642, Morgan L. Taschuk152, Kenji Tatsuno89, Simon Tavaré223,643, Darrin F. Taylor113, Amaro Taylor-Weiner8, Jon W. Teague49, Bin Tean Teh180,592,640,644,645, Varsha Tembe246, Javier Temes104,105, Kevin Thai76, Sarah P. Thayer393, Nina Thiessen30, Gilles Thomas646, Sarah Thomas221, Alan Thompson221, Alastair M. Thompson633, John F. Thompson211, R. Houston Thompson647, Heather Thorne103, Leigh B. Thorne176, Adrian Thorogood424, Grace Tiao8, Nebojsa Tijanic284, Lee E. Timms272, Roberto Tirabosco648, Marta Tojo106, Stefania Tommasi649, Christopher W. Toon170, Umut H. Toprak48,650, David Torrents57,81, Giampaolo Tortora651,652, Jörg Tost653, Yasushi Totoki118, David Townend654, Nadia Traficante103, Isabelle Treilleux655,656, Jean-Rémi Trotta61, Lorenz H. P. Trümper469, Ming Tsao124,539, Tatsuhiko Tsunoda183,657,658,659, Jose M. C. Tubio104,105,106, Olga Tucker660, Richard Turkington661, Daniel J. Turner513, Andrew Tutt323, Masaki Ueno376, Naoto T. Ueno662, Christopher Umbricht151,213,663, Husen M. Umer305,664, Timothy J. Underwood665, Lara Urban59,60, Tomoko Urushidate616, Tetsuo Ushiku339, Liis Uusküla-Reimand666,667, Alfonso Valencia57,81, David J. Van Den Berg166, Steven Van Laere307, Peter Van Loo290,291, Erwin G. Van Meir668, Gert G. Van den Eynden307, Theodorus Van der Kwast123, Naveen Vasudev137, Miguel Vazquez57,669, Ravikiran Vedururu267, Umadevi Veluvolu518, Shankar Vembu490,670, Lieven P. C. Verbeke506,671, Peter Vermeulen307, Clare Verrill351,672, Alain Viari177, David Vicente57, Caterina Vicentini177, K. Vijay Raghavan365, Juris Viksna673, Ricardo E. Vilain674, Izar Villasante57, Anne Vincent-Salomon635, Tapio Visakorpi190, Douglas Voet8, Paresh Vyas311,351, Ignacio Vázquez-García49,86,675,676, Nick M. Waddell209, Nicola Waddell209,311, Claes Wadelius677, Lina Wadi6, Rabea Wagener111,112, Jeremiah A. Wala8,14,82, Jian Wang56, Jiayin Wang1,40,66, Linghua Wang12, Qi Wang465, Wenyi Wang21, Yumeng Wang21, Zhining Wang220, Paul M. Waring523, Hans-Jörg Warnatz483, Jonathan Warrell5,19, Anne Y. Warren352,678, Sebastian M. Waszak60, David C. Wedge49,294,679, Dieter Weichenhan345, Paul Weinberger680, John N. Weinstein38, Joachim Weischenfeldt60,83,84, Daniel J. Weisenberger166, Ian Welch681, Michael C. Wendl1,10,11, Johannes Werner47,85, Justin P. Whalley61,682, David A. Wheeler12,13, Hayley C. Whitaker117, Dennis Wigle683, Matthew D. Wilkerson518, Ashley Williams244, James S. Wilmott211, Gavin W. Wilson6,148, Julie M. Wilson148, Richard K. Wilson1,684, Boris Winterhoff685, Jeffrey A. Wintersinger17,127,384, Maciej Wiznerowicz686,687, Stephan Wolf688, Bernice H. Wong689, Tina Wong1,30, Winghing Wong690, Youngchoon Woo250, Scott Wood209,311, Bradly G. Wouters44, Adam J. Wright6, Derek W. Wright133,691, Mark H. Wright217, Chin-Lee Wu72, Dai-Ying Wu285, Guanming Wu692, Jianmin Wu170, Kui Wu56,396, Yang Wu179,180, Zhenggang Wu64, Liu Xi12, Tian Xia693, Qian Xiang76, Xiao Xiao66, Rui Xing497, Heng Xiong56,396, Qinying Xu209,311, Yanxun Xu694, Hong Xue64, Shinichi Yachida118,695, Sergei Yakneen60, Rui Yamaguchi375, Takafumi N. Yamaguchi6, Masakazu Yamamoto120, Shogo Yamamoto89, Hiroki Yamaue376, Fan Yang490, Huanming Yang56, Jean Y. Yang696, Liming Yang220, Lixing Yang697, Shanlin Yang306, Tsun-Po Yang270, Yang Yang369, Xiaotong Yao408,698, Marie-Laure Yaspo483, Lucy Yates49, Christina Yau156, Chen Ye56,396, Kai Ye40,41, Venkata D. Yellapantula20,86, Christopher J. Yoon249, Sung-Soo Yoon463, Fouad Yousif6, Jun Yu699, Kaixian Yu700, Willie Yu701, Yingyan Yu702, Ke Yuan223,510,703, Yuan Yuan21, Denis Yuen6, Takashi Yugawa617, Christina K. Yung76, Olga Zaikova704, Jorge Zamora49,104,105,106, Marc Zapatka397, Jean C. Zenklusen220, Thorsten Zenz67, Nikolajs Zeps705,706, Cheng-Zhong Zhang8,707, Fan Zhang381, Hailei Zhang8, Hongwei Zhang494, Hongxin Zhang121, Jiashan Zhang220, Jing Zhang5, Junjun Zhang76, Xiuqing Zhang56, Xuanping Zhang66,369, Yan Zhang5,708,709, Zemin Zhang381,710, Zhongming Zhao711, Liangtao Zheng381, Xiuqing Zheng381, Wanding Zhou615, Yong Zhou56, Bin Zhu240, Hongtu Zhu700,712, Jingchun Zhu24, Shida Zhu56,396, Lihua Zou713, Xueqing Zou49, Anna deFazio246,247,714, Nicholas van As221, Carolien H. M. van Deurzen715, Marc J. van de Vijver523, L. van’t Veer716 & Christian von Mering433,717, 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.
Published: 2020
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12. Activation of hedgehog signaling associates with early disease progression in chronic lymphocytic leukemia

Author: Kelly A. Frazer, John Douglas Mcpherson, Thomas J. Hudson, Emanuela M. Ghia, Laura Z. Rassenti, Erin N. Smith, Donna Neuberg, Fouad Yousif, Alejandro Toro Blanco, Olivier Harismendy, and Thomas J. Kipps
Subjects: Adult, Male, 0301 basic medicine, Pyridines, Chronic lymphocytic leukemia, Immunology, medicine.disease_cause, Biochemistry, Zinc Finger Protein GLI1, 03 medical and health sciences, 0302 clinical medicine, GLI1, immune system diseases, hemic and lymphatic diseases, Cytotoxic T cell, Medicine, Humans, Hedgehog Proteins, Hedgehog, Aged, Aged, 80 and over, Mutation, Lymphoid Neoplasia, biology, integumentary system, Gene Expression Regulation, Leukemic, business.industry, Cell Biology, Hematology, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Hedgehog signaling pathway, Leukemia, Pyrimidines, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Disease Progression, Female, IGHV@, business, Signal Transduction
Abstract: Targeted sequencing of 103 leukemia-associated genes in leukemia cells from 841 treatment-naive patients with chronic lymphocytic leukemia (CLL) identified 89 (11%) patients as having CLL cells with mutations in genes encoding proteins that putatively are involved in hedgehog (Hh) signaling. Consistent with this finding, there was a significant association between the presence of these mutations and the expression of GLI1 (χ2 test, P < .0001), reflecting activation of the Hh pathway. However, we discovered that 38% of cases without identified mutations also were GLI1+. Patients with GLI1+ CLL cells had a shorter median treatment-free survival than patients with CLL cells lacking expression of GLI1 independent of IGHV mutation status. We found that GANT61, a small molecule that can inhibit GLI1, was highly cytotoxic for GLI1+ CLL cells relative to that of CLL cells without GLI1. Collectively, this study shows that a large proportion of patients have CLL cells with activated Hh signaling, which is associated with early disease progression and enhanced sensitivity to inhibition of GLI1.
Published: 2019

13. Regional perturbation of gene transcription is associated with intrachromosomal rearrangements and gene fusion transcripts in high grade ovarian cancer

Author: Fouad Yousif, Robert Rottapel, Fernando Suarez, Kyle E. Francis, John Douglas Mcpherson, Lincoln Stein, Josee Normand, Paul M. Krzyzanowski, Tim Beck, Jose La Rose, and Fabrice Sircoulomb
Subjects: 0301 basic medicine, Oncogene Proteins, Fusion, Protein domain, lcsh:Medicine, Computational biology, Biology, Article, Fusion gene, Transcriptome, 03 medical and health sciences, Chromosome Breakpoints, 0302 clinical medicine, Rare Diseases, Clinical Research, Biomarkers, Tumor, Genetics, Coding region, Humans, 2.1 Biological and endogenous factors, Aetiology, lcsh:Science, Fusion, Gene, Cancer, Ovarian Neoplasms, Oncogene Proteins, Neoplastic, Multidisciplinary, Tumor, lcsh:R, Human Genome, High-Throughput Nucleotide Sequencing, 3. Good health, Ovarian Cancer, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Gene Expression Regulation, Cancer cell, lcsh:Q, Female, Signal transduction, Gene Fusion, Neoplasm Grading, Reprogramming, 030217 neurology & neurosurgery, Biomarkers, Biotechnology
Abstract: Genomic rearrangements are a hallmark of cancer biology and progression, allowing cells to rapidly transform through alterations in regulatory structures, changes in expression patterns, reprogramming of signaling pathways, and creation of novel transcripts via gene fusion events. Though functional gene fusions encoding oncogenic proteins are the most dramatic outcomes of genomic rearrangements, we investigated the relationship between rearrangements evidenced by fusion transcripts and local expression changes in cancer using transcriptome data alone. 9,953 gene fusion predictions from 418 primary serious ovarian cancer tumors were analyzed, identifying depletions of gene fusion breakpoints within coding regions of fused genes as well as an N-terminal enrichment of breakpoints within fused genes. We identified 48 genes with significant fusion-associated upregulation and furthermore demonstrate that significant regional overexpression of intact genes in patient transcriptomes occurs within 1 megabase of 78 novel gene fusions that function as central markers of these regions. We reveal that cancer transcriptomes select for gene fusions that preserve protein and protein domain coding potential. The association of gene fusion transcripts with neighboring gene overexpression supports rearrangements as mechanism through which cancer cells remodel their transcriptomes and identifies a new way to utilize gene fusions as indicators of regional expression changes in diseased cells with only transcriptomic data.
Published: 2019

14. Abstract IA-018: Molecular landmarks of tumor hypoxia across cancer types

Author: Vincent Huang, Shadrielle Melijah G. Espiritu, Tina Vujcic, Lydia Y Liu, Vinayak Bhandari, Melvin L.K. Chua, Jessica Ray, Julie Livingstone, Lawrence E. Heisler, Emilie Lalonde, Yu-Jia Shiah, Veronica Y. Sabelnykova, Robert G. Bristow, Theodorus van der Kwast, Xiaoyong Huang, Paul C. Boutros, Stanley K. Liu, Fouad Yousif, Christianne Hoey, Michael Fraser, Cindy Q. Yao, Takafumi N. Yamaguchi, and Robert Lesurf
Subjects: Genome instability, Cancer Research, Chromothripsis, Tumor hypoxia, Cancer, Biology, Hypoxia (medical), medicine.disease, Primary tumor, Prostate cancer, Oncology, Cancer research, medicine, biology.protein, PTEN, medicine.symptom
Abstract: Many primary tumor sub-regions have low levels of molecular oxygen, termed hypoxia. Hypoxic tumors are at elevated risk for local failure and distant metastasis, but the molecular hallmarks of tumor hypoxia remain poorly defined. To fill this gap, we quantified hypoxia in 8,006 tumors across 19 tumor types. In ten tumor types, hypoxia was associated with elevated genomic instability. In all 19 tumor types, hypoxic tumors exhibited characteristic driver mutation signatures. We observed widespread hypoxia-associated dysregulation of miRNAs across cancers and functionally validated miR-133a-3p as a hypoxia-modulated miRNA. In localized prostate cancer, hypoxia was associated with elevated rates of chromothripsis, allelic loss of PTEN and shorter telomeres. These associations are particularly enriched in polyclonal tumors, representing a constellation of features resembling tumor nimbosus – an aggressive cellular phenotype. Overall, this work establishes that tumor hypoxia may drive aggressive molecular features across cancers and shape the clinical trajectory of individual tumors. Citation Format: Vinayak Bhandari, Christianne Hoey, Lydia Liu, Emilie Lalonde, Jessica Ray, Julie Livingstone, Robert Lesurf, Yu-Jia Shiah, Tina Vujcic, Xiaoyong Huang, Shadrielle M.G. Espiritu, Lawrence E. Heisler, Fouad Yousif, Vincent Huang, Takafumi N. Yamaguchi, Cindy Q. Yao, Veronica Y. Sabelnykova, Michael Fraser, Melvin L.K. Chua, Theodorus van der Kwast, Stanley K. Liu, Paul C. Boutros, Robert G. Bristow. Molecular landmarks of tumor hypoxia across cancer types [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-018.
Published: 2021
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15. Widespread and Functional RNA Circularization in Localized Prostate Cancer

Author: Musaddeque Ahmed, Jiansheng Guan, Yong Zeng, Cenk Sahinalp, Jouhyun Jeon, Youri Hoogstrate, Michèle Orain, Lawrence E. Heisler, Stanley K. Liu, Sujun Chen, Junjie Tony Hua, Natalie S. Fox, Remond J.A. Fijneman, Vincent Huang, Anna Lapuk, Adrien Foucal, Robert G. Bristow, Valérie Picard, Colin Collins, Julie Livingstone, Yuzhe Zhang, Vinayak Bhandari, Hélène Hovington, Melvin L.K. Chua, Jessica Petricca, Felix Y. Feng, Yves Fradet, Jixi Li, Xue Wu, Housheng Hansen He, Fraser Soares, Stas Volik, Alain Bergeron, Nilgun Donmez, Michael Fraser, Mark de Jong, Bernard Têtu, Miranda Wang, Malgorzata A. Komor, Paul C. Boutros, Teng Fei, Theodorus van der Kwast, Louis Lacombe, Yu Jia Shiah, Haiyang Guo, Fouad Yousif, Guido Jenster, Yang W. Shao, Xin Xu, Cardiology, and Urology
Subjects: Male, RNA, Untranslated, Polyadenylation, RNA Splicing, RNA-Seq, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Circular RNA, medicine, Humans, 030304 developmental biology, 0303 health sciences, Sequence Analysis, RNA, Gene Expression Profiling, Prostate, Cancer, RNA, Prostatic Neoplasms, RNA, Circular, Genetic Profile, Non-coding RNA, medicine.disease, 3. Good health, MicroRNAs, Editorial Commentary, HEK293 Cells, 030217 neurology & neurosurgery
Abstract: The cancer transcriptome is remarkably complex, including low-abundance transcripts, many not polyadenylated. To fully characterize the transcriptome of localized prostate cancer, we performed ultra-deep total RNA-seq on 144 tumors with rich clinical annotation. This revealed a linear transcriptomic subtype associated with the aggressive intraductal carcinoma sub-histology and a fusion profile that differentiates localized from metastatic disease. Analysis of back-splicing events showed widespread RNA circularization, with the average tumor expressing 7,232 circular RNAs (circRNAs). The degree of circRNA production was correlated to disease progression in multiple patient cohorts. Loss-of-function screening identified 11.3% of highly abundant circRNAs as essential for cell proliferation; for ∼90% of these, their parental linear transcripts were not essential. Individual circRNAs can have distinct functions, with circCSNK1G3 promoting cell growth by interacting with miR-181. These data advocate for adoption of ultra-deep RNA-seq without poly-A selection to interrogate both linear and circular transcriptomes.
Published: 2019

16. Molecular landmarks of tumor hypoxia across cancer types

Author: Vinayak Bhandari, Christianne Hoey, Veronica Y. Sabelnykova, Michael Fraser, Robert G. Bristow, Robert Lesurf, Julie Livingstone, Melvin L.K. Chua, Tina Vujcic, Yu-Jia Shiah, Lydia Y Liu, Emilie Lalonde, Vincent Huang, Lawrence E. Heisler, Xiaoyong Huang, Shadrielle Melijah G. Espiritu, Fouad Yousif, Paul C. Boutros, Theodorus van der Kwast, Cindy Q. Yao, Stanley K. Liu, Takafumi N. Yamaguchi, and Jessica Ray
Subjects: Genome instability, Male, Genomic Instability, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Cell Line, Tumor, microRNA, Genetics, medicine, PTEN, Humans, Hypoxia, Alleles, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Chromothripsis, Tumor hypoxia, biology, Gene Expression Profiling, PTEN Phosphohydrolase, Prostatic Neoplasms, Hypoxia (medical), Telomere, medicine.disease, Gene Expression Regulation, Neoplastic, MicroRNAs, PC-3 Cells, Cancer research, biology.protein, Tumor Hypoxia, medicine.symptom, 030217 neurology & neurosurgery
Abstract: Many primary-tumor subregions have low levels of molecular oxygen, termed hypoxia. Hypoxic tumors are at elevated risk for local failure and distant metastasis, but the molecular hallmarks of tumor hypoxia remain poorly defined. To fill this gap, we quantified hypoxia in 8,006 tumors across 19 tumor types. In ten tumor types, hypoxia was associated with elevated genomic instability. In all 19 tumor types, hypoxic tumors exhibited characteristic driver-mutation signatures. We observed widespread hypoxia-associated dysregulation of microRNAs (miRNAs) across cancers and functionally validated miR-133a-3p as a hypoxia-modulated miRNA. In localized prostate cancer, hypoxia was associated with elevated rates of chromothripsis, allelic loss of PTEN and shorter telomeres. These associations are particularly enriched in polyclonal tumors, representing a constellation of features resembling tumor nimbosus, an aggressive cellular phenotype. Overall, this work establishes that tumor hypoxia may drive aggressive molecular features across cancers and shape the clinical trajectory of individual tumors.
Published: 2018

17. The Origins and Consequences of Localized and Global Somatic Hypermutation

Author: Fan F, Fouad Yousif, Park Dh, Stephenie D. Prokopec, Szyca L, Christopher M. Lalansingh, Ren X. Sun, and Paul C. Boutros
Subjects: Genetics, APOBEC, 0303 health sciences, Mutation rate, Somatic hypermutation, Cancer, Biology, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, CDKN2A, 030220 oncology & carcinogenesis, Kataegis, Mutation (genetic algorithm), medicine, Gene, 030304 developmental biology
Abstract: Cancer is a disease of the genome, but the dramatic inter-patient variability in mutation number is poorly understood. Tumours of the same type can differ by orders of magnitude in their mutation rate. To understand potential drivers and consequences of the underlying heterogeneity in mutation rate across tumours, we evaluated both local and global measures of mutation density: both single-stranded and double-stranded DNA breaks in 2,460 tumours of 38 cancer types. We find that SCNAs in thousands of genes are associated with elevated rates of point-mutations, while similarly point-mutation patterns in dozens of genes are associated with specific patterns of DNA double-stranded breaks. These candidate drivers of mutation density are enriched for known cancer drivers, and preferentially occur early in tumour evolution, appearing clonally in all cells of a tumour. To supplement this understanding of global mutation density, we developed and validated a tool called SeqKat to identify localized “rainstorms” of point-mutations (kataegis). We show that rates of kataegis differ by four orders of magnitude across tumour types, with malignant lymphomas showing the highest. Tumours withTP53mutations were 2.6-times more likely to harbour a kataegic event than those without, and 239 SCNAs were associated with elevated rates of kataegis, including loss of the tumour-suppressorCDKN2A. We identify novel subtypes of kataegic events not associated with aberrant APOBEC activity, and find that these are localized to specific cellular regions, enriched for MYC-target genes. Kataegic events were associated with patient survival in some, but not all tumour types, highlighting a combination of global and tumour-type specific effects. Taken together, we reveal a landscape of genes driving localized and tumour-specific hyper-mutation, and reveal novel mutational processes at play in specific tumour types.
Published: 2018
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18. Abstract P2-05-05: A four gene signature predicts anthracycline benefit: Evidence from the BR9601 and MA5 breast cancer trials

Author: Chris Twelves, Fouad Yousif, John M. S. Bartlett, Melanie Spears, Nicola Lyttle, Lois E. Shepherd, Mark Levine, Alison F. Munro, and Kathleen I. Pritchard
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Pathology, Predictive marker, Anthracycline, business.industry, Hazard ratio, Area under the curve, Cancer, Gene signature, medicine.disease, Breast cancer, Internal medicine, Cohort, Medicine, business
Abstract: Background: Chromosome instability (CIN) in solid tumours is associated with poor prognosis and results in numerical and structural chromosomal aberrations. Recent evidence from both the BR9601 and MA.5 trials has demonstrated CEP17 duplication as a predictive marker of anthracycline benefit. CIN25 and CIN70 gene expression profiles have previously been published and predict survival response. An analysis of the BR9601 and MA5 clinical trials was performed to test the role of CIN gene expression signatures as a marker of anthracycline sensitivity. Methods: RNA was extracted from patients in both the BR9601 and MA5 studies and analysed through Nanostring technology. Log-rank analyses explored the prognostic values of the signatures on distant relapse-free survival (DRFS). Cox-regression models tested independent prognostic value on DRFS in the presence of treatment, age, tumour size, nodal status, ER status and grade, and treatment by marker interactions. Results: Of the 761 samples available from the BR9601 and MA5 cohorts we successfully analysed 703 (92.4%). High CIN25 and CIN70 scores were associated with age (p A more limited set of genes that reflected CIN was established by examining the expression profile of the genes and clustering them. The combined cohort was split into a 60% training and 40% validation set. The area under the curve (AUC) was calculated and the gene signature with the greatest AUC was selected and termed CIN4. Patients with low CIN4 score benefited from anthracycline treatment compared to those that had high CIN4 score (HR 2.72, 95% CI 1.48-5.02, p=0.001). No significant benefit with CMF treatment was observed in (HR: 1.02, 95% CI 0.58-1.82, p=0.92). After multivariate analysis the treatment by marker interaction for CIN4 had a hazard ratio of 2.10 (95% CI 2.18-30.38, p= 0.001). Conclusion: High CIN70 and CIN25 scores were associated with an aggressive phenotype and showed a potential increased sensitivity to anthracycline therapy compared to those with low CIN scores. CIN4 was an independent predictor of anthracycline benefit for DRFS. However, further work in larger patient cohorts such as NEAT is warranted. Citation Format: Melanie Spears, Nicola S Lyttle, Fouad Yousif, Alison F Munro, Christopher Twelves, Kathleen I Pritchard, Mark N Levine, Lois Shepherd, John MS Bartlett. A four gene signature predicts anthracycline benefit: Evidence from the BR9601 and MA5 breast cancer trials [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-05.
Published: 2015
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19. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia

Author: Liran I. Shlush, Sasan Zandi, Amanda Mitchell, Weihsu Claire Chen, Joseph M. Brandwein, Vikas Gupta, James A. Kennedy, Aaron D. Schimmer, Andre C. Schuh, Karen W. Yee, Jessica L. McLeod, Monica Doedens, Jessie J. F. Medeiros, Rene Marke, Hyeoung Joon Kim, Kwon Lee, John D. McPherson, Thomas J. Hudson, The HALT Pan-Leukemia Gene Panel Consortium, Andrew M. K. Brown, Fouad Yousif, Quang M. Trinh, Lincoln D. Stein, Mark D. Minden, Jean C. Y. Wang, and John E. Dick
Subjects: Myeloid, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], T-Lymphocytes, Cellular differentiation, Drug Resistance, HALT Pan-Leukemia Gene Panel Consortium, DNA Methyltransferase 3A, Mice, 0302 clinical medicine, hemic and lymphatic diseases, 2.1 Biological and endogenous factors, DNA (Cytosine-5-)-Methyltransferases, Aetiology, Cancer, Pediatric, 0303 health sciences, Leukemia, Multidisciplinary, Remission Induction, Nuclear Proteins, Cell Differentiation, Hematology, Isocitrate Dehydrogenase, 3. Good health, Leukemia, Myeloid, Acute, Haematopoiesis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Heterografts, Female, Stem Cell Research - Nonembryonic - Non-Human, Stem cell, Nucleophosmin, Cell Division, NPM1, Childhood Leukemia, Pediatric Cancer, General Science & Technology, Acute, Biology, SCID, Article, 03 medical and health sciences, Rare Diseases, Cancer stem cell, Genetics, medicine, Animals, Humans, Cell Lineage, 030304 developmental biology, Progenitor, Hematopoietic Stem Cells, Stem Cell Research, medicine.disease, Clone Cells, Hematopoiesis, Mutation, Immunology, Inbred NOD, Neoplasm, Neoplasm Transplantation
Abstract: Item does not contain fulltext In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3A(mut)) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3A(mut)-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3A(mut) arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance.
Published: 2014
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20. Abstract 3771: Oncogenes and tumour-suppressors drive differential retinoblastoma evolution

Author: Diane Rushlow, Hilary Racher, Julie Livingstone, Shadrielle Melijah G. Espiritu, Donco Matveski, Doroto H. Sendorek, Stephenie D. Prokopec, John D. Watson, Adriana Salcedo, Fouad Yousif, Paul C. Boutros, and Brenda L. Gallie
Subjects: Cancer Research, Oncology, law, Retinoblastoma, Cancer research, medicine, Suppressor, Biology, medicine.disease, Differential (mathematics), law.invention
Abstract: Unlike any other tumour type, retinoblastomas can be driven by only two tumour-initiating events: bi-allelic loss of the tumour suppressor RB1 or amplification of the MYCN oncogene. These mutations drive morphologically indistinguishable tumours that arise at different ages, providing a unique model system to evaluate the influence of initiating mutation on tumour evolution. We performed high-resolution copy number analysis of 101 retinoblastoma and whole genome sequencing of 23. These data reveal that different initiating mutations cause probabilistic changes in somatic point and copy number mutations, but large changes in genomic rearrangements and mitochondrial number. Independent of the initiating mutation, retinoblastomas harbour multiple subclonal populations that preferentially accrue point mutations after subclonal diversification. These subclonal structures suggest caution when choosing chemotherapeutic strategies for primary treatment. Overall, initiating mutations influence evolutionary trajectory more than specific driver mutations: RB1- and MYCN-driven tumours harbour distinct mutational processes, sequences of mutation acquisition and patterns of subclonal diversification. These data show how tumour-initiating mutations drive clinical behaviour by subtly biasing multiple evolutionary processes. Validation in other tumour types is underway. Citation Format: Adriana Salcedo, John D. Watson, Hilary Racher, Diane Rushlow, Shadrielle Melijah G. Espiritu, Doroto H. Sendorek, Stephenie D. Prokopec, Donco Matveski, Fouad Yousif, Julie Livingstone, Brenda L. Gallie, Paul C. Boutros. Oncogenes and tumour-suppressors drive differential retinoblastoma evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3771.
Published: 2019
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21. The molecular hallmarks and clinical consequences of tumor hypoxia in prostate cancer

Author: Shadrielle Espirritu, Lawrence E. Heisler, Lydia Y Liu, Fouad Yousif, Stanley K. Liu, Paul C. Boutros, Veronica Y. Sabelnykova, Theodorus van der Kwast, Julie Livingstone, Emilie Lalonde, Michael Fraser, Robert G. Bristow, Bhandari Vinayak, Takafumi N. Yamaguchi, Vincent Huang, Yu-Jia Shiah, and Melvin L.K. Chua
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Tumor hypoxia, business.industry, medicine.disease, Prostate cancer, medicine.anatomical_structure, Prostate, Internal medicine, medicine, Treatment decision making, Stage (cooking), business
Abstract: 81 Background: Localised prostate cancers are classified into risk-groups using clinical measurements like grade and stage to inform treatment decisions. However, these groupings are imprecise: ~30% of intermediate-risk patients suffer relapse of their disease despite precision image-guided radiotherapy or radical prostatectomy. One reason for this variability in response to treatment is the underlying cellular and molecular heterogeneity of tumours. Prostate tumour cells exist within a microenvironment characterized by gradients of oxygen levels and prostate tumours with low levels of oxygen (hypoxia) have poor clinical outcomes. Methods: Hypoxia was measured using multiple mRNA-based signatures. We examined 548 patients with localised prostate cancer and statistically assessed the association of hypoxia with copy-number alterations (CNAs), single-nucleotide variants (SNVs), genomic rearrangements, focal genomic events ( i.e. kataegis, chromothripsis), telomere length, clinical indices ( i.e. grade, stage) and subclonal architecture. Results: Elevated hypoxia was associated with allelic loss of PTEN, higher rates of chromothripsis and intraductal and cribriform carcinoma (IDC-CA). To translate these findings into a biomarker for prostate cancer precision medicine, we integrated tumour microenvironmental data with genomic and pathological information to stratify patients into distinct prognostic groups. Patients with localized prostate cancer that have polyclonal tumours with elevated hypoxia, allelic loss of PTEN and IDC-CA were at the highest risk of rapid biochemical failure (P = 3.48 x10-3, Logrank test) and metastasis (P = 4.61 x 10-3, Logrank test), even after controlling for T-category, Gleason score and pre-treatment PSA. Conclusions: These data suggest that the aggressiveness of prostate cancers is driven by the interplay of the tumour microenvironment, tumour evolutionary trajectories and its genomic mutational profile.
Published: 2019
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22. Genomic hallmarks of localized, non-indolent prostate cancer

Author: Michèle Orain, Yu Jia Shiah, Ken Kron, Lawrence E. Heisler, Mathieu Lupien, Xuemei Luo, Andre P. Masella, Michelle Sam, Paul C. Boutros, Shaylan K. Govind, Daryl Waggott, Veronica Y. Sabelnykova, Natalie S. Fox, Musaddeque Ahmed, Julia F. Hopkins, Lee Timms, Clement Fung, Francis Nguyen, Zhiyuan Wang, Taryne Chong, Alain Bergeron, Julie Livingstone, Yves Fradet, Melvin L.K. Chua, Timothy Beck, Alexander Murison, Bernard Têtu, Ada Wong, Ren X. Sun, Constance H. Li, Kathleen E. Houlahan, John Douglas Mcpherson, Cenk Sahinalp, Housheng Hansen He, Junyan Zhang, Robert G. Bristow, Jeremy Johns, Neil E. Fleshner, Alejandro Berlin, Michelle Chan-Seng-Yue, Christine P'ng, Nicholas Buchner, Alister D'Costa, Richard de Borja, Xihui Lin, Louis Lacombe, Jeffrey Green, Hélène Hovington, Vincent Huang, Kenneth C. Chu, Haiying Kong, Emilie Lalonde, Nicholas J. Harding, Syed Haider, Esther Jung, Colin Collins, Shadrielle Melijah G. Espiritu, Takafumi N. Yamaguchi, Bryan Lo, Michael Xie, Valérie Picard, Michael Fraser, Stephenie D. Prokopec, Christopher I Cooper, Fouad Yousif, Theodorus van der Kwast, Robert E. Denroche, Alice Meng, Dominique Trudel, and Alan Dal Pra
Subjects: 0301 basic medicine, Male, DNA Copy Number Variations, Somatic hypermutation, Genomics, Disease, Biology, Bioinformatics, 03 medical and health sciences, Prostate cancer, Recurrence, medicine, Humans, Exome, Neoplasm Metastasis, 610 Medicine & health, Chromothripsis, Multidisciplinary, Genome, Human, Prostatic Neoplasms, Methylation, DNA Methylation, medicine.disease, Prognosis, Human genetics, Prostatic Neoplasms, Castration-Resistant, 030104 developmental biology, DNA methylation, Mutation, Cancer research
Abstract: Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.
Published: 2017
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23. Postnatally Acquired Mutations Underlie the Progression of Transient Leukemia to Myeloid Leukemia of Down Syndrome

Author: Sagi Abelson, John Douglas Mcpherson, Fouad Yousif, Sanaz Manteghi, Jian Chen, Johann K. Hitzler, and Yue Li
Subjects: Mutation, Cohesin complex, Immunology, Clone (cell biology), Myeloid leukemia, GATA1, Cell Biology, Hematology, Gene mutation, Biology, medicine.disease_cause, Biochemistry, Myeloid Leukemia Associated with Down Syndrome, CTCF, medicine, Cancer research
Abstract: INTRODUCTION . Transient Leukemia (TL; also termed Transient Myeloproliferative disorder, TMD, and Transient Abnormal Myelopoiesis, TAM) occurs in 10-30% of newborns with Down syndrome (DS). Approx. 20% of infants with TL go on to develop acute myeloid leukemia of DS (ML-DS), typically within the first four years of life. Somatic, clone-specific mutations of GATA1 are found both in the blasts of TL and ML-DS, are concordant within the same individual and thought to function as initiating event in the development of ML-DS. In contrast, additional mutations of cohesin complex and related genes (e.g. RAD21, STAG2, CTCF), epigenetic regulators (e. g. EZH2) and signal transducers (e.g. within RAS, JAK signaling pathways) have been identified only in ML-DS blasts and are thought to cooperate with mutant GATA1 in the progression from TL to ML-DS. It is not known whether these cooperating mutations already mark a minor subclone of TL blasts at birth - allowing, at least in principle, a genetic risk stratification of TL - or are acquired postnatally during the first four years of life. OBJECTIVES . We tested the functional impact of impaired function of cohesin complex genes, CTCF and EZH2 on the progression of TL to ML-DS. We asked if mutations representing putative genetic progression events were already detectable at birth in a minor clone of TL blasts or were acquired postnatally (during the first four years of life). METHODS. The spectrum of GATA1 and cooperating mutations was determined by whole exome sequencing in fractions of TL and ML-DS blasts sorted from blood and bone marrow samples of five patients who had successively developed both disorders including one with a relapse of ML-DS. Corresponding normal T lymphocyte fractions of each patient at the stage of TL and ML-DS served as controls. Numbers of blasts harboring specific mutations were quantified by digital droplet PCR (BioRad, Inc.). Primary TL cells were transduced with lentivirus encoding shRNA (pLVX-shRNA, Clontech, Inc.) to suppress expression of cohesin complex genes, CTCF and EZH2 and intrafemurally injected into 8 week old NSG recipient mice. Engraftment in the bone marrow was assessed 8 weeks later by flow cytometry and GATA1 mutational analysis and compared to TL cells transduced with control vector. RESULTS. TL blasts harbored fewer mutations than those of ML-DS. GATA1 mutations were concordant in TL and ML-DS blasts in the same patient, consistent with development of ML-DS from subclone of TL. Knockdown of RAD21 expression in primary TL blasts, mimicking loss of function mutation of a cohesin complex gene, resulted in significantly increased engraftment of transduced cells in xenograft recipients compared to controls. This finding is consistent with RAD21 loss of function mutations playing the role of a progression event. Mutations of cohesin complex genes (SMC1A, STAG2, RAD21), NRAS and other putative cooperating mutations (with mutant GATA1) were not detectable in any sample of primary TL blasts by either whole exome sequencing or digital droplet PCR. The same result was obtained with control T lymphocytes sorted from TL samples. ML-DS blasts in one case were oligo-clonal with regard to cohesin complex gene mutations. Relapse in this patient arose from a minor clone as defined by cohesin complex gene mutations; mutations of NRAS, KNASL1 and SMC1A were present in ML-DS blasts but absent at relapse. CONCLUSIONS . Increased engraftment of TL cells with suppressed RAD21 expression is consistent with a model in which RAD21 loss of function mutations function as a progression event in the development of ML-DS. Absence of detectable cohesin complex gene mutations and other putative cooperating events in TL blasts suggests these mutations are acquired during the first four years of life and do not mark a minor clone of TL blasts present at birth. Genomic screening of TL blasts at birth therefore is unlikely to predict the risk for development of ML-DS. Disclosures No relevant conflicts of interest to declare.
Published: 2018
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24. Abstract 2432: The genomic consequences of tumor hypoxia in human cancers

Author: Robert G. Bristow, Yu-Jia Shiah, Melvin L.K. Chua, Theodorus H. van der Kwast, Paul C. Boutros, Julie Livingstone, Shadrielle Melijah G. Espiritu, Vincent Huang, Vinayak Bhandari, Emilie Lalonde, Veronica Y. Sabelnykova, Lawrence E. Heisler, Fouad Yousif, Takafumi N Yamaguchi, Michael Fraser, and Lydia Y Liu
Subjects: Cancer Research, Oncology, Tumor hypoxia, business.industry, Cancer research, Medicine, business
Abstract: Introduction: Localized prostate cancers are classified into risk-groups using clinical measurements like grade and stage to inform treatment decisions. However, these groupings are imprecise: ~30% of intermediate-risk patients suffer relapse of their disease despite precision image-guided radiotherapy or radical prostatectomy. One reason for this variability in response to treatment is the underlying cellular and molecular heterogeneity of tumors. Prostate tumor cells exist within a microenvironment characterized by gradients of oxygen levels and prostate tumors with low levels of oxygen (hypoxia) have poor clinical outcomes. Methods and Results: To understand the correlates of hypoxia in cancer we conducted a pan-cancer analysis of copy number alterations (CNAs) and single nucleotide variants (SNVs) across 19 cancer types. We measured hypoxia using multiple mRNA-based signatures and discovered numerous CNAs and SNVs enriched or depleted in hypoxic tumors, highlighting the role of hypoxia in shaping the genomic landscape of multiple tumor types. Next, we examined 548 patients with localized prostate cancer and statistically assessed the association of hypoxia with CNAs, SNVs, genomic rearrangements, focal genomic events (i.e. kataegis, chromothripsis), telomere length, clinical indices (i.e. grade, stage) and subclonal architecture. Tumor hypoxia is associated with specific CNAs and SNVs in prostate cancer driver genes. To translate these findings into a biomarker for prostate cancer precision medicine, we integrated tumor microenvironmental data with genomic and pathological information to stratify patients into distinct prognostic groups. Impact: These data suggest that the aggressiveness of cancers is driven by the interplay of the tumor microenvironment and its genomic mutational profile. Citation Format: Vinayak Bhandari, Shadrielle M. Espiritu, Lydia Y. Liu, Emilie Lalonde, Takafumi N. Yamaguchi, Lawrence E. Heisler, Julie Livingstone, Vincent Huang, Yu-Jia Shiah, Veronica Y. Sabelnykova, Fouad Yousif, Melvin L. Chua, Michael Fraser, Theodorus van der Kwast, Paul C. Boutros, Robert G. Bristow. The genomic consequences of tumor hypoxia in human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2432.
Published: 2018
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25. The Evolutionary Landscape of Localized Prostate Cancers Drives Clinical Aggression

Author: Julie Livingstone, Kathleen E. Houlahan, Emilie Lalonde, Yulia Rubanova, Vinayak Bhandari, Takafumi N. Yamaguchi, Vincent Huang, Lesia M. Szyca, Lydia Y Liu, Quaid Morris, Fouad Yousif, Melvin L.K. Chua, Paul C. Boutros, Constance H. Li, Natalie S. Fox, Jeff Wintersinger, Erle Holgersen, Alexandre Rouette, Adriana Salcedo, Michael Fraser, Shadrielle Melijah G. Espiritu, Robert G. Bristow, Theodorus van der Kwast, and Lawrence E. Heisler
Subjects: Male, 0301 basic medicine, Ubiquitin-Protein Ligases, Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Prostate cancer, Prostate, Biopsy, Biomarkers, Tumor, medicine, Humans, Prospective Studies, Prospective cohort study, Gene, PI3K/AKT/mTOR pathway, Proportional Hazards Models, Homeodomain Proteins, Manchester Cancer Research Centre, medicine.diagnostic_test, TOR Serine-Threonine Kinases, ResearchInstitutes_Networks_Beacons/mcrc, Point mutation, High-Throughput Nucleotide Sequencing, Prostatic Neoplasms, medicine.disease, 3. Good health, Retinoblastoma Binding Proteins, 030104 developmental biology, medicine.anatomical_structure, Monoclonal, Cancer research, Neoplasm Grading, Neoplasm Recurrence, Local, Transcription Factors
Abstract: The majority of newly diagnosed prostate cancers are slow growing, with a long natural life history. Yet a subset can metastasize with lethal consequences. We reconstructed the phylogenies of 293 localized prostate tumors linked to clinical outcome data. Multiple subclones were detected in 59% of patients, and specific subclonal architectures associate with adverse clinicopathological features. Early tumor development is characterized by point mutations and deletions followed by later subclonal amplifications and changes in trinucleotide mutational signatures. Specific genes are selectively mutated prior to or following subclonal diversification, including MTOR, NKX3-1, and RB1. Patients with low-risk monoclonal tumors rarely relapse after primary therapy (7%), while those with high-risk polyclonal tumors frequently do (61%). The presence of multiple subclones in an index biopsy may be necessary, but not sufficient, for relapse of localized prostate cancer, suggesting that evolution-aware biomarkers should be studied in prospective studies of low-risk tumors suitable for active surveillance.
Published: 2018
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26. A four gene signature predicts benefit from anthracyclines:Evidence from the BR9601 and MA.5 clinical trials

Author: Mark Levine, Kathleen I. Pritchard, Alison F. Munro, Paul C. Boutros, Chris Twelves, John M. S. Bartlett, Nicola Lyttle, Fouad Yousif, Lois E. Shepherd, and Melanie Spears
Subjects: Oncology, Multivariate analysis, Messenger, Anthracycline, Bioinformatics, Breast cancer, Antibiotics, Antineoplastic Combined Chemotherapy Protocols, Medicine, Anthracyclines, predictive biomarker, Univariate analysis, Tumor, Antibiotics, Antineoplastic, Predictive marker, Reverse Transcriptase Polymerase Chain Reaction, Hazard ratio, Middle Aged, Prognosis, Antineoplastic, 3. Good health, Gene Expression Regulation, Neoplastic, Survival Rate, Predictive biomarker, Local, Female, Signal Transduction, Research Paper, medicine.medical_specialty, Oncology and Carcinogenesis, Breast Neoplasms, Real-Time Polymerase Chain Reaction, anthracycline, breast cancer, Chromosomal Instability, Internal medicine, Biomarkers, Tumor, Humans, RNA, Messenger, Neoplasm Staging, Proportional Hazards Models, Neoplastic, business.industry, Gene Expression Profiling, Chromosome instability, Gene signature, medicine.disease, Clinical trial, Neoplasm Recurrence, Gene Expression Regulation, RNA, Neoplasm Grading, Neoplasm Recurrence, Local, chromosome instability, business, Biomarkers, Follow-Up Studies
Abstract: Chromosome instability (CIN) in solid tumours results in multiple numerical and structural chromosomal aberrations and is associated with poor prognosis in multiple tumour types. Recent evidence demonstrated CEP17 duplication, a CIN marker, is a predictive marker of anthracycline benefit. An analysis of the BR9601 and MA.5 clinical trials was performed to test the role of existing CIN gene expression signatures as predictive markers of anthracycline sensitivity in breast cancer. Univariate analysis demonstrated, high CIN25 expression score was associated with improved distant relapse free survival (DRFS) (HR: 0.74, 95% CI 0.54-0.99, p = 0.046). High tumour CIN70 and CIN25 scores were associated with aggressive clinicopathological phenotype and increased sensitivity to anthracycline therapy compared to low CIN scores. However, in a prospectively planned multivariate analysis only pathological grade, nodal status and tumour size were significant predictors of outcome for CIN25/CIN70. A limited gene signature was generated, patients with low tumour CIN4 scores benefited from anthracycline treatment significantly more than those with high CIN4 scores (HR 0.37, 95% CI 0.20-0.56, p = 0.001). In multivariate analyses the treatment by marker interaction for CIN4/anthracyclines demonstrated hazard ratio of 0.35 (95% CI 0.15-0.80, p = 0.012) for DRFS. This data shows CIN4 is independent predictor of anthracycline benefit for DRFS in breast cancer.
Published: 2015
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27. Targeted sequencing in a phase III trial of luminal breast cancer: Identification of novel targets

Author: Lee Timms, Irina Kalatskaya, Quang M. Trinh, Karen Rothfels, Marija Milacic, Shawna Lee, Annette Hasenburg, John Douglas Mcpherson, Dirk G. Kieback, Paul C. Boutros, John M. S. Bartlett, Jane Bayani, Lawrence E. Heisler, Fouad Yousif, Nicholas Buchner, Lincoln Stein, Cheryl Crozier, Camilla Drake, and Daniel Rea
Subjects: Cancer Research, Breast cancer, Oncology, business.industry, Cancer genome, medicine, Computational biology, Bioinformatics, medicine.disease, business
Abstract: 505 Background: The International Cancer Genome Consortium and The Cancer Genome Atlas have had a global transformative impact on our understanding of cancer. These programs have mapped the genomic landscape of common and rare tumors setting the scene for a comprehensive change in the approach to cancer diagnosis and treatment. However, the task remains incomplete until these mutational events are linked to clinical outcomes in the context of current therapeutic intervention to drive future stratified medicine approaches. Methods: We performed targeted sequencing in patients from the Tamoxifen Exemestane Adjuvant Multicentre trial. DNA was extracted and a 101 gene panel analysed using a novel mutation calling pipeline. Both a priori and machine learning analyses were performed using distant recurrence free survival as the primary endpoint. Results: In 1,491 successfully analyzed samples 1,070 (71.76%) samples exhibited at least one single nucleotide mutation (range 0-94, 1.828+/-0.133, mean+/-s.e.). 98/101 genes were mutated in at least one patient. Only variants in PIK3CA, TP53, MLL3, CDH1 were detected in 5% or more of samples. Twenty genes were associated with increased risk of recurrence in multivariate analyses corrected for clinic-pathological variables, 50% of these genes were involved in transcriptional regulation or RNA/protein processing. In a multivariate analysis, two combined signalling modules were independently prognostic for residual risk following hormone therapy (HRvalidation 3.10 95%CI 1.78-5.40 and HRvalidation 2.70 95%CI 1.57-4.64). Conclusions: We successfully performed a signalling pathway-based targeted sequencing analysis within predefined signalling modules. In supervised and unsupervised analyses we identified multiple signalling cassettes linked to poor outcome in patients with ER+ve breast cancers treated with modern endocrine therapy in the context of a phase III clinical trial. These results identify novel candidates as targets to treat endocrine refractory breast cancers.
Published: 2017
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28. Spatial genomic heterogeneity within localized, multifocal prostate cancer

Author: Hanbo Chen, Julie Livingstone, Cherry Have, Thomas J. Hudson, Veronica Y. Sabelnykova, Ada Wong, Stephenie D. Prokopec, Timothy Beck, Shaylan K. Govind, Kenneth C. Chu, Gaetano Zafarana, Robert G. Bristow, Neil E. Fleshner, Alister D'Costa, Fouad Yousif, Jeremy Johns, James R. Hawley, Daryl Waggott, Lee Timms, John D. Watson, Colin Cooper, Paul C. Boutros, Bernard Têtu, Emilie Lalonde, Cenk Sahinalp, Dominique Trudel, Jenna Sykes, Esther Jung, David E. Neal, Trent T. Simmons, Faraz Hach, Michael Fraser, Christine P'ng, Robert E. Denroche, Lincoln Stein, Colin Collins, Xuemei Luo, Rosalind A. Eeles, Sohrab P. Shah, Melania Pintilie, Theodorus van der Kwast, Clement Fung, Francis Nguyen, Michelle Chan-Seng-Yue, Andrew M.K. Brown, John Douglas Mcpherson, Amin Zia, Alan Dal Pra, Nicholas J. Harding, Alice Meng, Lauren C. Chong, Philippe Lambin, Pablo H. Hennings-Yeomans, Richard de Borja, Nicholas Buchner, Andrew McPherson, Jianxin Wang, Yu Jia Shiah, Michelle Sam, Maud H.W. Starmans, Natalie S. Fox, Taryne Chong, Gregory M. Chen, Alejandro Berlin, Lakshmi Muthuswamy, Promovendi ODB, Radiotherapie, RS: GROW - Oncology, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
Subjects: Male, DNA Copy Number Variations, Genomics, Biology, Bioinformatics, Genome, Polymorphism, Single Nucleotide, DNA sequencing, Proto-Oncogene Proteins c-myc, Prostate cancer, Genetic Heterogeneity, Cell Line, Tumor, Genetics, medicine, Humans, Point Mutation, 610 Medicine & health, Gene, Genetic Association Studies, Genetic heterogeneity, Genome, Human, Point mutation, Cancer, Prostatic Neoplasms, Middle Aged, medicine.disease, Cancer research, Neoplasm Grading
Abstract: Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.
Published: 2014

29. Educational outcomes of The University of Toronto Visiting Professor Rounds Series

Author: Zaid Mammo, Wai Ching Lam, and Fouad Yousif
Subjects: Ontario, Medical education, Pediatrics, medicine.medical_specialty, Academic Medical Centers, Health Knowledge, Attitudes, Practice, Knowledge gain, business.industry, Decision Making, General Medicine, Ophthalmology, Practice change, Cross-Sectional Studies, Clinical decision making, Health Care Surveys, Teaching Rounds, Medicine, Humans, Education, Medical, Continuing, Clinical Competence, Educational Measurement, business, Societies, Medical, Computer-Assisted Instruction, Follow-Up Studies
Abstract: Objective To assess how the University of Toronto Visiting Professors Rounds Series (UTVPRS) influenced the knowledge, perceptions, and clinical decision making of Canadian ophthalmologists. Design Longitudinal cross-sectional. Participants Eight hundred and fifty ophthalmologists registered with the Canadian Ophthalmological Society. Methods Online surveys, using multiple-choice and reflection questions, were administered before and after online viewing of the University of Toronto Ophthalmology grand rounds as screencasts. Results At 18 months, 124 users registered and watched 429 screencasts. Most participants found UTVPRS to be organized and user friendly. Mean prescreencast correct scores were 1008 versus 1288 postscreencast ( p = 0.002). Postscreencast, 73% of participants replied in favour of changing future practice. Conclusions UTVPRS was well received with demonstrated knowledge gain and potential practice change. The long-term and patient-related outcomes of the results require further research.
Published: 2013

30. Abstract B18: Genomic analysis of pancreatic ductal adenocarcinoma

Author: Richard de Borja, Christine Ouellete, Michelle Sam, Lee Timms, Timothy Beck, Carson Holt, Rob Denroche, John Douglas Mcpherson, Lakshmi Muthuswamy, Kimberly Begley, Thomas J. Hudson, Lincoln Stein, Fouad Yousif, Christina K. Yung, Niloofar Arshadi, and Z. Zha
Subjects: Genetics, Candidate gene, Mutation, Pancreatic cancer, medicine, Cancer, KRAS, Ion semiconductor sequencing, Biology, medicine.disease, medicine.disease_cause, Exome, Deep sequencing
Abstract: Pancreatic cancer is the fifth leading cause of cancer deaths. Five-year survival rate is In our initial screen, whole-exome sequencing of 33 primary PDAC tumors and matched controls has been performed on the Illumina HiSeq 2000. Sequence alignment and variant calling have been performed using Novoalign and GATK, respectively. After manual review and validation on the Ion Torrent platform, we have identified 648 somatic mutations, 471 of which are non-silent mutations that impact 444 genes. Our results confirm several known mutations in PDAC such as KRAS, p53 and SMAD4. However, their mutation frequencies are lower than expected due to tumor cellularity. We have also screened for copy number alterations (CNAs) using Illumina Omni1-Quad BeadChip. Analysis was performed using Genome Studio, KSseg and PennCNV. In the 33 primary tumors, a median of 90 regions with copy number gain, copy number loss, or copy-neutral LOH have been detected per sample. Median genomic lengths are 19Mb and 20Mb in regions with copy number gain and loss, respectively. Annotation of the altered regions has identified 9152 protein-coding genes, miRNA and non-coding RNA that are altered in 4 or more tumors. To identify the pathways that contribute to PDAC, we have analyzed the genes with somatic mutations or CNAs by means of a functional interaction (FI) network. The FI network consists of curated pathways from Reactome and other databases and a high confidence set of functional interactions predicted by machine learning techniques. A PDAC-specific subnetwork is constructed by projecting the altered genes onto the FI network, and subsequently analyzed by a community clustering algorithm to identify network modules. These modules have been identified as KRAS, p53, TGFβ, Hedgehog, Integrin, Cadherin, Wnt, Rho GTPase and G-protein signaling pathways. While our effort in identifying driver mutations is ongoing, our initial screen has identified candidate genes that will be targeted for deep sequencing in all primary tumors. We will continue to perform whole-exome sequencing of other primary tumors along with xenografts derived from some of the primaries and cell lines derived from some of the xenografts. In addition, whole-genome sequencing of selected specimens is being performed to complement the exome data. The wealth of data will help to characterize the genomic abnormalities in PDAC. Citation Format: Christina K. Yung, Christine Ouellete, Lee Timms, Michelle Sam, Kimberly Begley, Thomas J. Hudson, John D. McPherson, Lincoln D. Stein, Timothy Beck, Lakshmi Muthuswamy, Richard De Borja, Carson Holt, Rob Denroche, Fouad Yousif, Zheng Zha, Niloofar Arshadi. Genomic analysis of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B18.
Published: 2012
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31. Abstract B13: Whole-genome mutation landscape in pancreatic ductal adenocarcinoma

Author: Richard de Borja, Tim Beck, Lakshmi Muthuswamy, Carson Holt, Kimberly Begley, Lee Timms, Christina K. Yung, Irinia Kalatskaya, Niloofar Arshadi, Robert E. Denroche, John Douglas Mcpherson, Lincoln Stein, Christine Ouelltt, Michelle Sam, Bojan Losic, Fouad Yousif, and Thomas J. Hudson
Subjects: Whole genome sequencing, Genetics, Mutation, Pancreatic cancer, DNA methylation, medicine, Biology, medicine.disease, medicine.disease_cause, Genome, Gene, Primary tumor, Deep sequencing
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a rare cancer with a very high mortality rate. Because it is extremely difficult to detect at an early stage; PDAC tumors often spread to regional lymph nodes or distant metastases by the time they are diagnosed. Published reports have already identified a number of chromosomal alterations at many genomic levels; however PDAC still lacks a comprehensive catalogue for the whole genome mutation spectrum. The goal of our study is to annotate all types of identifiable genomic aberrations based on whole genome sequencing of 5 PDAC tumors. It is a common knowledge that surgical primary tissues of PDAC have very low tumor content. Hence, for our study all five primary tumors have been modeled as xenografts using NOD-SCID mice to enrich for tumor cells. Here, we report on the cancer-specific genome alterations in 5 PDAC tumors and show that xenograft models do represent genomic landscape of primary tumors. All samples were whole-genome sequenced using Illumina HiSeq to give a minimum coverage of 30X. We have developed an analysis pipeline to identify somatic single nucleotide variations (SNVs) using The Genome Analysis Tool Kit (GATK), copy number alterations (CNAs) using KSseg (in-house CNV algorithm) and structural variations using Geometric Analysis of Structural Variants (GASV). A number of filters have been implemented to separate germline variants and mouse derived contamination from the cancer specific somatic variation. Our analysis has identified an average of 1527 SNVs, 1555 INDELs, and 53 CNAs per PDAC genome (combined for primary and xenograft). All somatic SNVs were verified using Ion Torrent based sequencing technology with a verification rate of 93%. CNAs were verified using Nimblegen 2.1M Array-based Comparative Genome Hybridization technology, and produced a verification rate of greater than 98% for losses and 60-97% for gains. We also observed a high level of overlap between primary tumor and xenograft samples, with 84% of total primary tumor SNVs and 61% of INDELS (called across all samples) being found in the correlating xenograft genome. After verification of SNVs by deep sequencing, we observe an additional 50% of SNVs that were called only in the xenograft samples validate in the primary sample. Our results show that the somatic single nucleotide mutation rate is in the range of 1 - 4 SNVs/Mb and there is a statistically significant increase in the G>T transversions. It is well known that methylated CpG dinucleotides are the preferred sites for G > T transversions and we are investigating the role played by DNA methylation alterations. All somatic variants were annotated using an in-house software package based on Sequence Ontology classification of variant effects to integrate different types of variations and provide a functional interpretation. Our analysis has identified 290 genes that are functionally impacted in 4 or more genomes by any type of mutation. They include 6 known oncogenes, 10 protein kinases, 9 cell differentiation markers, 17 transcription factors and 6 cytokines and growth factors. Functional enrichment analysis on this gene set using MSigDB v3.0 database shows important cancer-related pathways including the NK cells pathway, the Adherens junctions interactions pathway, and the axon guidance signaling pathway. Citation Format: Carson Holt, Fouad Yousif, Lee Timms, Michelle Sam, Kimberly Begley, Thomas Hudson, John D. McPherson, Lincoln D. Stein, Lakshmi B. Muthuswamy, Christina Yung, Tim Beck, Bojan Losic, Niloofar Arshadi, Christine Ouelltt, Irinia Kalatskaya, Richard de Borja, Robert Denroche. Whole-genome mutation landscape in pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B13.
Published: 2012
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32. Abstract 2966: The mutational landscape of localized gleason 6 and 7 prostate cancer

Author: Alice Meng, Xuemei Luo, Robert G. Bristow, Dominique Trudel, Lee Timms, Yves Fradet, Colin Collins, Shaylan K. Govind, Clement Fung, Francis Nguyen, Paul C. Boutros, Hélène Hovington, Alejandro Berlin, Junyan Zhang, Stephenie D. Prokopec, Michael Fraser, Haiying Kong, Louis Lacombe, Ada Wong, Vincent Huang, Julie Livingstone, Christopher I Cooper, Andre P. Masella, Michelle Sam, Taryne Chong, Veronica Y. Sabelnykova, Kathleen E. Houlahan, John Douglas Mcpherson, Nicholas J. Harding, Takafumi N. Yamaguchi, Michèle Orain, Lawrence E. Heisler, Nicholas Buchner, Jeremy Johns, Natalie S. Fox, Alister D'Costa, Fouad Yousif, Xihui Lin, Richard de Borja, Bryan Lo, Christine P'ng, Kenneth C. Chu, Emilie Lalonde, Theodorus H. van der Kwast, Timothy E. Beck, Thomas J. Hudson, Michael Xie, Robert E. Denroche, Bernard Têtu, and Valérie Picard
Subjects: Oncology, Genetics, Cancer Research, medicine.medical_specialty, Chromothripsis, business.industry, medicine.disease, Prostate cancer, Prostate tumours, medicine.anatomical_structure, Prostate, Kataegis, Localized disease, Internal medicine, medicine, business
Abstract: Prostate cancer (CaP) remains the most common male malignancy worldwide, leading to over 300,000 deaths per year. In Western countries, most prostate tumours are diagnosed while they are confined to the prostate and have relatively indolent histology, as assessed by the Gleason Score (GS). CaP is a C-class tumour, characterized by large number of driver copy-number aberrations and genomic rearrangements. Therefore, while previous sequencing studies have focused largely on the coding regions of late-stage disease, herein we comprehensively characterized the copy-number profiles of 250 localized prostate cancers and analyzed the whole genomes of 124 matched tumour/normal pairs derived from patients with GS6 and GS7 prostate cancer. Using this – the largest whole-genome sequencing dataset of prostate cancer to date – we confirm the C-class character of the disease and identify strong genomic subtypes that stretch across multiple types of somatic alteration, including SNVs, CNAs and genomic rearrangements. We provide the first assessments of localized hyper-mutation phenomena (chromothripsis and kataegis) in prostate cancer, and identify specific genes driving higher levels of these hyper-mutations. We identify unexpected biases in the location and role of both non-coding SNVs and genomic rearrangements, including clear association with epigenetic processes, and with genome-wide profiling of methylation in 92 samples. Finally, we demonstrate a stark paucity of clinically-actionable mutations in localized GS6 and GS7 disease, even lacking those common in high-risk localized disease, indicating that novel therapeutic development against the recurrent targets identified here will be key to allowing less-aggressive, targeted treatment of early-stage disease. Citation Format: Michael E. Fraser, Veronica Y. Sabelnykova, Takafumi N. Yamaguchi, Alice Meng, Lawrence E. Heisler, Junyan Zhang, Julie Livingstone, Vincent Huang, Andre P. Masella, Fouad Yousif, Michael Xie, Nicholas J. Harding, Xihui Lin, Haiying Kong, Stephenie D. Prokopec, Alejandro Berlin, Dominique Trudel, Xuemei Luo, Timothy E. Beck, Richard de Borja, Alister D'Costa, Robert E. Denroche, Natalie S. Fox, Emilie Lalonde, Ada Wong, Taryne Chong, Michelle Sam, Jeremy Johns, Lee Timms, Nicholas Buchner, Michele Orain, Valerie Picard, Helene Hovington, Kenneth C. Chu, Christine P'ng, Bryan Lo, Francis Nguyen, Kathleen E. Houlahan, Christopher Cooper, Shaylan K. Govind, Clement Fung, Louis Lacombe, Colin C. Collins, Yves Fradet, Bernard Tetu, Theodorus van der Kwast, John McPherson, Thomas J. Hudson, Rob G. Bristow, Paul Boutros. The mutational landscape of localized gleason 6 and 7 prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2966. doi:10.1158/1538-7445.AM2015-2966
Published: 2015
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33. Origin and diversification of the human parasite Schistosoma mansoni

Author: Jess A T, Morgan, Randall J, Dejong, Grace O, Adeoye, Ebenezer D O, Ansa, Constança S, Barbosa, Philippe, Brémond, Italo M, Cesari, Nathalie, Charbonnel, Lygia R, Corrêa, Godefroy, Coulibaly, Paulo Sérgio, D'Andrea, Cecilia Pereira, De Souza, Michael J, Doenhoff, Sharon, File, Mohamed A, Idris, R Nino, Incani, Philippe, Jarne, Diana M S, Karanja, Francis, Kazibwe, John, Kpikpi, Nicholas J S, Lwambo, Amadou, Mabaye, Luiz A, Magalhães, Asanteli, Makundi, Hélène, Moné, Gabriel, Mouahid, Gerald M, Muchemi, Ben N, Mungai, Mariama, Séne, Vaughan, Southgate, Louis Albert Tchuem, Tchuenté, Andre, Théron, Fouad, Yousif, Eliana M, Zanotti-Magalhães, Gerald M, Mkoji, Eric S, Loker, Parasitologie fonctionnelle et évolutive [2003-2006] (PFE), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Perpignan Via Domitia (UPVD)
Subjects: Male, Geography, Biomphalaria, Arabia, Genetic Variation, Schistosoma mansoni, Sequence Analysis, DNA, DNA, Helminth, South America, DNA, Mitochondrial, Phylogeography, Caribbean Region, Haplotypes, schistosomiasis, parasitic diseases, Africa, [SDE]Environmental Sciences, Madagascar, Animals, Humans, Female, slave trade, Phylogeny, Brazil
Abstract: International audience; Schistosoma mansoni is the most widespread of the human-infecting schistosomes, present in 54 countries, predominantly in Africa, but also in Madagascar, the Arabian Peninsula, and the Neotropics. Adult-stage parasites that infect humans are also occasionally recovered from baboons, rodents, and other mammals. Larval stages of the parasite are dependent upon certain species of freshwater snails in the genus Biomphalaria, which largely determine the parasite's geographical range. How S. mansoni genetic diversity is distributed geographically and among isolates using different hosts has never been examined with DNA sequence data. Here we describe the global phylogeography of S. mansoni using more than 2500 bp of mitochondrial DNA (mtDNA) from 143 parasites collected in 53 geographically widespread localities. Considerable within-species mtDNA diversity was found, with 85 unique haplotypes grouping into five distinct lineages. Geographical separation, and not host use, appears to be the most important factor in the diversification of the parasite. East African specimens showed a remarkable amount of variation, comprising three clades and basal members of a fourth, strongly suggesting an East African origin for the parasite 0.30-0.43 million years ago, a time frame that follows the arrival of its snail host. Less but still substantial variation was found in the rest of Africa. A recent colonization of the New World is supported by finding only seven closely related New World haplotypes which have West African affinities. All Brazilian isolates have nearly identical mtDNA haplotypes, suggesting a founder effect from the establishment and spread of the parasite in this large country
Published: 2005
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34. Differences of Somatic Mutations and Gene Expression in Blasts of Transient Leukemia and Acute Myeloid Leukemia of Down Syndrome

Author: Jian Chen, John Douglas Mcpherson, Timothy Beck, Fouad Yousif, and Johann K. Hitzler
Subjects: Down syndrome, Immunology, Clone (cell biology), Cancer, Myeloid leukemia, GATA1, Cell Biology, Hematology, Gene mutation, Biology, medicine.disease, Biochemistry, Germline mutation, hemic and lymphatic diseases, medicine, Exome sequencing
Abstract: Background: Transient leukemia (TL) occurs in 30% of newborns with Down syndrome (DS) and typically resolves spontaneously. Approximately 20% of infants with TL go on to develop acute myeloid leukemia of DS (DS-AML) within the first four years of life. The blasts of both TL and DS-AML harbor somatic mutations of GATA1 . The objective of this study was to identify additional genetic events, which associated with the progression of TL to DS-AML. Methods: Leukemic blasts of TL, DS-AML and normal T lymphocytes were sorted from blood and bone marrow samples of five patients who successively developed both disorders. In addition, blasts of one patient with subsequent relapse of DS-AML were analyzed. Mutational spectrum and gene expression and were determined by exome sequencing and RNASeq (Illumina HiSeq2000). The presence of mutations, which were identified with this approach in DS-AML blasts, was examined by droplet digital PCR in TL blasts (BioRad QX200). Results: Blasts of TL overall harbored fewer mutations than those of DS-AML. Mutations of cohesin and RAS pathway genes were identified in a subset of DS-AML but not TL. In the patient who developed a relapse, different cohesin gene mutations were detected at initial diagnosis of AML and relapse; a minor clone present at initial diagnosis of AML emerged as the predominant clone at relapse. Concordant somatic GATA1 mutations were present in both TL and DS-AML blasts derived from the same patient. In contrast, other genetic events, which were detected in DS-AML blasts by exome sequencing, were confirmed to be absent in TL (by droplet digital PCR). The majority of differentially expressed genes showed higher expression levels in blasts of TL compared to DS-AML. They included genes encoding chemokines and related to IL1 and TGFb signaling. Conclusions: The pathogenic sequence starting with TL and culminating in AML is uniquely initiated in children with DS by somatic mutation of GATA1. In contrast, the events associated with the transformation of TL to DS-AML resemble progression factors also found in non-DS AML. These progression events were not detectable even in minor subclones of TL suggesting they are acquired after the onset of TL. This research was supported by funding from the Canadian Cancer Society Research Institute and Ontario Institute for Cancer Research. Disclosures No relevant conflicts of interest to declare.
Published: 2014
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35. Correction: Corrigendum: Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia

Author: Liran I. Shlush, Sasan Zandi, Amanda Mitchell, Weihsu Claire Chen, Joseph M. Brandwein, Vikas Gupta, James A. Kennedy, Aaron D. Schimmer, Andre C. Schuh, Karen W. Yee, Jessica L. McLeod, Monica Doedens, Jessie J. F. Medeiros, Rene Marke, Hyeoung Joon Kim, Kwon Lee, John D. McPherson, Thomas J. Hudson, The HALT Pan-Leukemia Gene Panel Consortium, Andrew M. K. Brown, Fouad Yousif, Quang M. Trinh, Lincoln D. Stein, Mark D. Minden, Jean C. Y. Wang, and John E. Dick
Subjects: Oncology, medicine.medical_specialty, Haematopoiesis, Multidisciplinary, Tumour heterogeneity, Cancer stem cell, business.industry, Internal medicine, Cancer genetics, medicine, Identification (biology), Stem cell, business
Abstract: Nature 506, 328–333 (2014); doi:10.1038/nature13038 Author Fouad Yousif (of the Ontario Institute for Cancer Research, Toronto, Canada) should have been included in the author list after Andrew M. K. Brown with affiliation number 7 and listed in the Author Contributions as performing and analysing targeted sequencing; these omissions have been corrected in the online versions of this Article.
Published: 2014
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36. Abstract 2003: A molecular portrait of potentially curable prostate cancer

Author: Michelle Chan-Seng-Yue, Amin Zia, Francis Nguyen, Thomas J. Hudson, Gaetano Zafarana, Natalie S. Fox, Fouad Yousif, Lee Timms, Hanbert Chen, Paul C. Boutros, Shaylan K. Govind, Maud H.W. Starmans, Lincoln Stein, Melania Pintilie, Michael Fraser, Rob Denroche, Theodorus van der Kwast, Stanislav Volik, Jeremy Johns, Andrew M.K. Brown, Nicholas J. Harding, Colin Collins, Alice Meng, Ada Wong, Pablo H. Hennings-Yeomans, Nicholas Buchner, Timothy Beck, Michelle Sam, Emilie Lalonde, Taryne Chong, Lakshmi Muthuswamy, Neil Fleshner, John Douglas Mcpherson, Richard de Borja, Jianxin Wang, Dominique Trudel, and Robert G. Bristow
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Pathology, business.industry, Prostatectomy, Genetic heterogeneity, medicine.medical_treatment, Concordance, Cancer, medicine.disease, Prostate cancer, genomic DNA, Internal medicine, medicine, Personalized medicine, business, SNP array
Abstract: Intermediate risk prostate cancer (CaP) with Gleason score (GS) of 7 show up to 100x variability in genetic instability. As CaP is multifocal and likely multiclonal, there is a need to characterize heterogeneity for patient stratification, which would increase the ability to act on genomic information by adding adjuvant therapies to offset systemic occult metastases that currently limit cure in ∼30% of patients. Individual genetic portraits could be used to improve cure on combined clinical-molecular staging criteria. We undertook a pilot study to assess the genetic heterogeneity of potentially curable GS=7 CaP. We selected 10 men with GS=7 CaP; 5 treated with external beam radiotherapy (frozen pre-treatment biopsies) and 5 treated with radical prostatectomy (RadP, frozen tumour). Additionally, DNA from 18 distinct formalin-fixed, paraffin-embedded (FFPE) foci from the 5 RadP were analysed. Each of these 28 foci were subjected to whole-genome sequencing (WGS) and OncoScan SNP arrays to yield comprehensive genetic profiles. mRNA expression was evaluated on frozen RadP by microarray. Germline DNA from whole-blood was also analysed. Following independent pathology reviews and manual macro-dissection of tumour areas of ≥70% cellularity, WGS (≥50x tumour, ≥30x germline) was performed on as little as 50 ng genomic DNA, and OncoScan arrays were performed using as little as 30ng DNA using either amplified or innate genomic DNA. Regions of CaP in FFPE RadP were recorded using a tissue map to identify independent malignant foci, and ERG immunostaining was performed to assist in the identification. In cases where ERG-positive and -negative foci were adjacent, ERG staining was repeated on an un-stained slide to confirm separate foci based on 3D multi-section analyses. ERG fusion status was also assessed in frozen samples by aCGH or IHC. Validation of SNVs via SNP array and deep-resequencing showed ∼99% accuracy. Tumour cellularity was estimated using Qpure and was >60% for all samples. Phylogenetic techniques were used to demonstrate clear multi-clonality in two tumours. Across all tumours, ∼50% of SNVs were specific to an individual tumour-region. Phylogenies were confirmed with both SNVs and CNAs, but CNAs generally exhibited greater concordance amongst different regions of the same tumour. Some previously observed recurrent mutations were previously identified as recurrent in CaP (e.g. SPOP), and the overall mutation rate for intermediate-risk CaP was only somewhat below that reported for castrate-resistant disease (11,230 somatic SNVs per tumour). Our studies support the concept that a complete characterization of inter- and intra-CaP heterogeneity is possible in fresh and archival tissues; the latter is important for correlations to clinical outcome. These approaches can then be streamlined for high-throughput analyses within personalized medicine laboratories leading to “point of care” molecular tests and individualization of therapy. Citation Format: Michael E. Fraser, Richard de Borja, Dominique Trudel, Nicholas J. Harding, Pablo H. Hennings-Yeomans, Alice Meng, Emilie R. Lalonde, Andrew Brown, Natalie S. Fox, Taryne Chong, Amin Zia, Michelle Sam, Jianxin Wang, Michelle A. Chan-Seng-Yue, Jeremy Johns, Lee Timms, Nicholas Buchner, Ada Wong, Fouad Yousif, Rob Denroche, Gaetano Zafarana, Maud HW Starmans, Hanbert Chen, Shaylan Govind, Francis Nguyen, Melania Pintilie, Neil Fleshner, Stanislav Volik, Lakshmi Muthuswamy, Colin C. Collins, Thomas J. Hudson, Lincoln D. Stein, Timothy Beck, John D. McPherson, Theodorus van der Kwast, Paul C. Boutros, Rob G. Bristow. A molecular portrait of potentially curable prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2003. doi:10.1158/1538-7445.AM2013-2003
Published: 2013
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37. Abstract 3184: Whole genome sequencing of low-input fresh frozen prostate cancer biopsies

Author: Lee Timms, Maud H.W. Starmans, John Douglas Mcpherson, Michelle Chan-Seng-Yue, Amin Zia, Timothy Beck, Lakshmi Muthuswamy, Michelle Sam, Theodorus van der Kwast, Alice Meng, Pablo H. Hennings-Yeomans, Jeremy Johns, Neil Fleshner, Emilie Lalonde, Robert G. Bristow, Lincoln Stein, Thomas J. Hudson, Fouad Yousif, Rob Denroche, Richard de Borja, Jianxin Wang, Melania Pintilie, Gaetano Zafarana, Michael Fraser, Colin Collins, Paul C. Boutros, and Taryne Chong
Subjects: Whole genome sequencing, Oncology, Cancer Research, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Cancer, Bioinformatics, medicine.disease, Malignancy, Genome, Prostate cancer, medicine.anatomical_structure, Prostate, Internal medicine, Biopsy, Medicine, business, Genotyping
Abstract: Prostate cancer is the most commonly diagnosed malignancy among men in the United States. Due to an aging population, prostate cancer incidence has been increasing, with an estimated 200,000 men being diagnosed in 2010 and more than 32,000 deaths resulting from this disease. Better predictors of patient prognosis and treatment outcome are required to individualize prostate cancer treatment. High-throughput genomic sequence-based approaches offer a unique opportunity to identify biomarkers of disease-progression, thereby enabling more individualized therapy. The Canadian Prostate Cancer Genome Network (CPC-GENE) is an outcomes-based initiative that will sequence 500 specimens from 350 prostate cancer patients over a 5-year time span. Previously, whole genome sequencing efforts from biopsy specimens have been hindered by insufficient quantities of extracted DNA required as input for sequencing library construction. As a proof of concept to demonstrate the ability to sequence low input amounts of DNA from prostate biopsies, whole genome sequencing has been initiated for 50 prostate tumor biopsy samples along with their matched blood-derived reference sample. An on-bead sample preparation protocol was optimized using decreasing quantities of input DNA and used to construct sequencing libraries from as low as 100ng of DNA derived from macrodissected fresh frozen prostate biopsies (>70% cellularity). Sequencing is performed on the Illumina HiSeq 2000 platform to generate coverage depths of 50x for tumor samples and 30x for reference samples. Following alignment using NovoAlign and variant-calling using GATK, we compared our results to genotyping-array results generated using the Affymetrix OncoScan platform. Single-nucleotide variants detected using arrays were validated >99% of the time by sequence data, confirming that the use of a low-input library did not hinder mutation detection. Sequencing does not exhibit significant genome-wide coverage biases, and CNV calls were compared between the genotyping arrays and the next-generation sequencing data. Outcomes from the sequencing and analysis of the initial 50 sample sets will similarly be applied over a 5-year period to characterize an additional 450 prostate specimens. The ability to whole genome sequence specimens where minimal amounts of extracted DNA exist presents new opportunities to sequence many samples previously deemed unusable, while also providing encouraging prospects for whole genome sequencing applications for future studies using biopsy specimens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3184. doi:1538-7445.AM2012-3184
Published: 2012
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38. Interaction of phenoxybenzamine with muscarinic receptors and calcium channels

Author: Fouad Yousif, David J. Triggle, R.A. Janis, and Peter J. Gengo
Subjects: Male, medicine.medical_specialty, Nifedipine, Phenoxybenzamine, Guinea Pigs, chemistry.chemical_element, Calcium, In Vitro Techniques, Tritium, Biochemistry, Ion Channels, Nitrendipine, Ileum, Internal medicine, Muscarinic acetylcholine receptor, medicine, Animals, Pharmacology, Voltage-dependent calcium channel, Chemistry, Antagonist, Muscarinic antagonist, Depolarization, Calcium Channel Blockers, Receptors, Muscarinic, Quinuclidinyl Benzilate, Endocrinology, Potassium, medicine.drug
Abstract: Phenoxybenzamine (POB, 10 −6 –10 −4 M) inhibited the responses of guinea pig ileal longitudinal smooth muscle to both muscarinic agonists and K + -depolarization but was more effective against the agonist-induced responses. POB inhibited binding of both the muscarinic antagonist [ 3 H]-quinuclidinyl benzilate (QNB) and the Ca 2+ channel antagonist [ 3 H]nitrendipine and was, paralleling its effects on mechanical responses, more effective against [ 3 H]QNB binding. POB reduced specific [ 3 H]QNB binding by a reduction in B max with no change in K D , but inhibited [ 3 H]nitrendipine binding by reducing k D with no effect on B max . It is suggested that the activity of POB against Ca 2+ channels may underlie the ability of POB, and other 2-halogenoethylamines, to inhibit a wide variety of apparently discrete pharmacological events.
Published: 1984

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