Author: "Teague, Jon W." - Searchworks@Jio Institute Digital Library Search Results

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194 results on '"Teague, Jon W."'

1. Geographic variation of mutagenic exposures in kidney cancer genomes

Author: Senkin, Sergey, Moody, Sarah, Díaz-Gay, Marcos, Abedi-Ardekani, Behnoush, Cattiaux, Thomas, Ferreiro-Iglesias, Aida, Wang, Jingwei, Fitzgerald, Stephen, Kazachkova, Mariya, Vangara, Raviteja, Le, Anh Phuong, Bergstrom, Erik N., Khandekar, Azhar, Otlu, Burçak, Cheema, Saamin, Latimer, Calli, Thomas, Emily, Atkins, Joshua Ronald, Smith-Byrne, Karl, Cortez Cardoso Penha, Ricardo, Carreira, Christine, Chopard, Priscilia, Gaborieau, Valérie, Keski-Rahkonen, Pekka, Jones, David, Teague, Jon W., Ferlicot, Sophie, Asgari, Mojgan, Sangkhathat, Surasak, Attawettayanon, Worapat, Świątkowska, Beata, Jarmalaite, Sonata, Sabaliauskaite, Rasa, Shibata, Tatsuhiro, Fukagawa, Akihiko, Mates, Dana, Jinga, Viorel, Rascu, Stefan, Mijuskovic, Mirjana, Savic, Slavisa, Milosavljevic, Sasa, Bartlett, John M. S., Albert, Monique, Phouthavongsy, Larry, Ashton-Prolla, Patricia, Botton, Mariana R., Silva Neto, Brasil, Bezerra, Stephania Martins, Curado, Maria Paula, Zequi, Stênio de Cássio, Reis, Rui Manuel, Faria, Eliney Ferreira, de Menezes, Nei Soares, Ferrari, Renata Spagnoli, Banks, Rosamonde E., Vasudev, Naveen S., Zaridze, David, Mukeriya, Anush, Shangina, Oxana, Matveev, Vsevolod, Foretova, Lenka, Navratilova, Marie, Holcatova, Ivana, Hornakova, Anna, Janout, Vladimir, Purdue, Mark P., Rothman, Nathaniel, Chanock, Stephen J., Ueland, Per Magne, Johansson, Mattias, McKay, James, Scelo, Ghislaine, Chanudet, Estelle, Humphreys, Laura, de Carvalho, Ana Carolina, Perdomo, Sandra, Alexandrov, Ludmil B., Stratton, Michael R., and Brennan, Paul
Published: 2024
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2. Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor

Author: Islam, SM Ashiqul, Díaz-Gay, Marcos, Wu, Yang, Barnes, Mark, Vangara, Raviteja, Bergstrom, Erik N, He, Yudou, Vella, Mike, Wang, Jingwei, Teague, Jon W, Clapham, Peter, Moody, Sarah, Senkin, Sergey, Li, Yun Rose, Riva, Laura, Zhang, Tongwu, Gruber, Andreas J, Steele, Christopher D, Otlu, Burçak, Khandekar, Azhar, Abbasi, Ammal, Humphreys, Laura, Syulyukina, Natalia, Brady, Samuel W, Alexandrov, Boian S, Pillay, Nischalan, Zhang, Jinghui, Adams, David J, Martincorena, Iñigo, Wedge, David C, Landi, Maria Teresa, Brennan, Paul, Stratton, Michael R, Rozen, Steven G, and Alexandrov, Ludmil B
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Genetics, Biotechnology, Tobacco Smoke and Health, Human Genome, Cancer, Prevention, Tobacco, Good Health and Well Being, cancer genomics, genomics, mutagenesis, mutational signatures
Abstract: Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for de novo extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures. Applying SigProfilerExtractor to 4,643 whole-genome- and 19,184 whole-exome-sequenced cancers reveals four novel signatures. Two of the signatures are confirmed in independent cohorts, and one of these signatures is associated with tobacco smoking. In summary, this report provides a reference tool for analysis of mutational signatures, a comprehensive benchmarking of bioinformatics tools for extracting signatures, and several novel mutational signatures, including one putatively attributed to direct tobacco smoking mutagenesis in bladder tissues.
Published: 2022

3. Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence

Author: Moody, Sarah, Senkin, Sergey, Islam, S. M. Ashiqul, Wang, Jingwei, Nasrollahzadeh, Dariush, Cortez Cardoso Penha, Ricardo, Fitzgerald, Stephen, Bergstrom, Erik N., Atkins, Joshua, He, Yudou, Khandekar, Azhar, Smith-Byrne, Karl, Carreira, Christine, Gaborieau, Valerie, Latimer, Calli, Thomas, Emily, Abnizova, Irina, Bucciarelli, Pauline E., Jones, David, Teague, Jon W., Abedi-Ardekani, Behnoush, Serra, Stefano, Scoazec, Jean-Yves, Saffar, Hiva, Azmoudeh-Ardalan, Farid, Sotoudeh, Masoud, Nikmanesh, Arash, Poustchi, Hossein, Niavarani, Ahmadreza, Gharavi, Samad, Eden, Michael, Richman, Paul, Campos, Lia S., Fitzgerald, Rebecca C., Ribeiro, Luis Felipe, Soares-Lima, Sheila Coelho, Dzamalala, Charles, Mmbaga, Blandina Theophil, Shibata, Tatsuhiro, Menya, Diana, Goldstein, Alisa M., Hu, Nan, Malekzadeh, Reza, Fazel, Abdolreza, McCormack, Valerie, McKay, James, Perdomo, Sandra, Scelo, Ghislaine, Chanudet, Estelle, Humphreys, Laura, Alexandrov, Ludmil B., Brennan, Paul, and Stratton, Michael R.
Published: 2021
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4. The driver landscape of sporadic chordoma.

Author: Tarpey, Patrick S, Behjati, Sam, Young, Matthew D, Martincorena, Inigo, Alexandrov, Ludmil B, Farndon, Sarah J, Guzzo, Charlotte, Hardy, Claire, Latimer, Calli, Butler, Adam P, Teague, Jon W, Shlien, Adam, Futreal, P Andrew, Shah, Sohrab, Bashashati, Ali, Jamshidi, Farzad, Nielsen, Torsten O, Huntsman, David, Baumhoer, Daniel, Brandner, Sebastian, Wunder, Jay, Dickson, Brendan, Cogswell, Patricia, Sommer, Josh, Phillips, Joanna J, Amary, M Fernanda, Tirabosco, Roberto, Pillay, Nischalan, Yip, Stephen, Stratton, Michael R, Flanagan, Adrienne M, and Campbell, Peter J
Subjects: Cell Line, Tumor, Humans, Chordoma, Bone Neoplasms, T-Box Domain Proteins, Fetal Proteins, Vesicular Transport Proteins, Case-Control Studies, Gene Duplication, Mutation, Polymorphism, Single Nucleotide, Phosphatidylinositol 3-Kinases, Class I Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Polymorphism, Single Nucleotide
Abstract: Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.
Published: 2017

5. A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing.

Author: Alioto, Tyler S, Buchhalter, Ivo, Derdak, Sophia, Hutter, Barbara, Eldridge, Matthew D, Hovig, Eivind, Heisler, Lawrence E, Beck, Timothy A, Simpson, Jared T, Tonon, Laurie, Sertier, Anne-Sophie, Patch, Ann-Marie, Jäger, Natalie, Ginsbach, Philip, Drews, Ruben, Paramasivam, Nagarajan, Kabbe, Rolf, Chotewutmontri, Sasithorn, Diessl, Nicolle, Previti, Christopher, Schmidt, Sabine, Brors, Benedikt, Feuerbach, Lars, Heinold, Michael, Gröbner, Susanne, Korshunov, Andrey, Tarpey, Patrick S, Butler, Adam P, Hinton, Jonathan, Jones, David, Menzies, Andrew, Raine, Keiran, Shepherd, Rebecca, Stebbings, Lucy, Teague, Jon W, Ribeca, Paolo, Giner, Francesc Castro, Beltran, Sergi, Raineri, Emanuele, Dabad, Marc, Heath, Simon C, Gut, Marta, Denroche, Robert E, Harding, Nicholas J, Yamaguchi, Takafumi N, Fujimoto, Akihiro, Nakagawa, Hidewaki, Quesada, Víctor, Valdés-Mas, Rafael, Nakken, Sigve, Vodák, Daniel, Bower, Lawrence, Lynch, Andrew G, Anderson, Charlotte L, Waddell, Nicola, Pearson, John V, Grimmond, Sean M, Peto, Myron, Spellman, Paul, He, Minghui, Kandoth, Cyriac, Lee, Semin, Zhang, John, Létourneau, Louis, Ma, Singer, Seth, Sahil, Torrents, David, Xi, Liu, Wheeler, David A, López-Otín, Carlos, Campo, Elías, Campbell, Peter J, Boutros, Paul C, Puente, Xose S, Gerhard, Daniela S, Pfister, Stefan M, McPherson, John D, Hudson, Thomas J, Schlesner, Matthias, Lichter, Peter, Eils, Roland, Jones, David TW, and Gut, Ivo G
Subjects: Humans, Medulloblastoma, Mutation, Genome, Human, Leukemia, Lymphoid, High-Throughput Nucleotide Sequencing, Genome, Human, Leukemia, Lymphoid
Abstract: As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines and validation methods. We show that using PCR-free methods and increasing sequencing depth to ∼ 100 × shows benefits, as long as the tumour:control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artefact-prone nature of the raw data and lack of standards for dealing with the artefacts. However, we show that, using the benchmark mutation set we have created, many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.
Published: 2015

6. The BioMart community portal: an innovative alternative to large, centralized data repositories.

Author: Smedley, Damian, Haider, Syed, Durinck, Steffen, Pandini, Luca, Provero, Paolo, Allen, James, Arnaiz, Olivier, Awedh, Mohammad Hamza, Baldock, Richard, Barbiera, Giulia, Bardou, Philippe, Beck, Tim, Blake, Andrew, Bonierbale, Merideth, Brookes, Anthony J, Bucci, Gabriele, Buetti, Iwan, Burge, Sarah, Cabau, Cédric, Carlson, Joseph W, Chelala, Claude, Chrysostomou, Charalambos, Cittaro, Davide, Collin, Olivier, Cordova, Raul, Cutts, Rosalind J, Dassi, Erik, Di Genova, Alex, Djari, Anis, Esposito, Anthony, Estrella, Heather, Eyras, Eduardo, Fernandez-Banet, Julio, Forbes, Simon, Free, Robert C, Fujisawa, Takatomo, Gadaleta, Emanuela, Garcia-Manteiga, Jose M, Goodstein, David, Gray, Kristian, Guerra-Assunção, José Afonso, Haggarty, Bernard, Han, Dong-Jin, Han, Byung Woo, Harris, Todd, Harshbarger, Jayson, Hastings, Robert K, Hayes, Richard D, Hoede, Claire, Hu, Shen, Hu, Zhi-Liang, Hutchins, Lucie, Kan, Zhengyan, Kawaji, Hideya, Keliet, Aminah, Kerhornou, Arnaud, Kim, Sunghoon, Kinsella, Rhoda, Klopp, Christophe, Kong, Lei, Lawson, Daniel, Lazarevic, Dejan, Lee, Ji-Hyun, Letellier, Thomas, Li, Chuan-Yun, Lio, Pietro, Liu, Chu-Jun, Luo, Jie, Maass, Alejandro, Mariette, Jerome, Maurel, Thomas, Merella, Stefania, Mohamed, Azza Mostafa, Moreews, Francois, Nabihoudine, Ibounyamine, Ndegwa, Nelson, Noirot, Céline, Perez-Llamas, Cristian, Primig, Michael, Quattrone, Alessandro, Quesneville, Hadi, Rambaldi, Davide, Reecy, James, Riba, Michela, Rosanoff, Steven, Saddiq, Amna Ali, Salas, Elisa, Sallou, Olivier, Shepherd, Rebecca, Simon, Reinhard, Sperling, Linda, Spooner, William, Staines, Daniel M, Steinbach, Delphine, Stone, Kevin, Stupka, Elia, Teague, Jon W, Dayem Ullah, Abu Z, Wang, Jun, and Ware, Doreen
Subjects: Humans, Neoplasms, Proteomics, Genomics, Internet, Database Management Systems, Developmental Biology, Environmental Sciences, Biological Sciences, Information and Computing Sciences
Abstract: The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations.
Published: 2015

7. Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups

Author: Bolli, Niccolo, Biancon, Giulia, Moarii, Matahi, Gimondi, Silvia, Li, Yilong, de Philippis, Chiara, Maura, Francesco, Sathiaseelan, Vijitha, Tai, Yu-Tzu, Mudie, Laura, O’Meara, Sarah, Raine, Keiran, Teague, Jon W., Butler, Adam P., Carniti, Cristiana, Gerstung, Moritz, Bagratuni, Tina, Kastritis, Efstathios, Dimopoulos, Meletios, Corradini, Paolo, Anderson, Kenneth C., Moreau, Philippe, Minvielle, Stephane, Campbell, Peter J., Papaemmanuil, Elli, Avet-Loiseau, Herve, and Munshi, Nikhil C.
Published: 2018
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8. Complex landscapes of somatic rearrangement in human breast cancer genomes

Author: Stephens, Philip J, McBride, David J, Lin, Meng-Lay, Varela, Ignacio, Pleasance, Erin D, Simpson, Jared T, Stebbings, Lucy A, Leroy, Catherine, Edkins, Sarah, Mudie, Laura J, Greenman, Chris D, Jia, Mingming, Latimer, Calli, Teague, Jon W, Lau, King Wai, Burton, John, Quail, Michael A, Swerdlow, Harold, Churcher, Carol, Natrajan, Rachael, Sieuwerts, Anieta M, Martens, John WM, Silver, Daniel P, Langerød, Anita, Russnes, Hege EG, Foekens, John A, Reis-Filho, Jorge S, van ’t Veer, Laura, Richardson, Andrea L, Børresen-Dale, Anne-Lise, Campbell, Peter J, Futreal, P Andrew, and Stratton, Michael R
Subjects: Cancer, Human Genome, Breast Cancer, Genetics, Aetiology, 2.1 Biological and endogenous factors, Breast Neoplasms, Cell Line, Tumor, Cells, Cultured, Chromosome Aberrations, DNA Breaks, Female, Gene Rearrangement, Genome, Human, Genomic Library, Humans, Sequence Analysis, DNA, General Science & Technology
Abstract: Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.
Published: 2009

9. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Author: Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Al-Shahrour, Fatima, Bailey, Peter J, Biankin, Andrew V, Boutros, Paul C, Campbell, Peter J, Chang, David K, Cooke, Susanna L, Deshpande, Vikram, Faltas, Bishoy M, Faquin, William C, Garraway, Levi, Getz, Gad, Grimmond, Sean M, Haider, Syed, Hoadley, Katherine A, Kaiser, Vera B, Kato, Mamoru, Kübler, Kirsten, Lazar, Alexander J, Li, Constance H, Louis, David N, Margolin, Adam, Martin, Sancha, Nahal-Bose, Hardeep K, Nielsen, G Petur, Nik-Zainal, Serena, Omberg, Larsson, P’ng, Christine, Perry, Marc D, Rheinbay, Esther, Rubin, Mark A, Semple, Colin A, Sgroi, Dennis C, Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D, Stobbe, Miranda D, Sun, Ren X, Thai, Kevin, Wright, Derek W, Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Morris, Quaid D, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlevaro-Fita, Joana, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chakravarty, Dimple, Chalmers, Don, Chan, Calvin Wing Yiu, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Ken, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Jung Kyoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshwar, Amit G, Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C, Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Fan, Daiming, Fan, Yu, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Feuerbach, Lars, Field, Matthew A, Fink, J Lynn, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Fonseca, Nuno A, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Frigola, Joan, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gallinger, Steven, Gambacorti-Passerini, Carlo, Gao, Jianjiong, Gao, Shengjie, Garred, Øystein, Garrison, Erik, Garsed, Dale W, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstein, Mark, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gonzalez-Perez, Abel, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Guo, Qianyun, Gupta, Manaswi, Gupta, Shailja, Gut, Ivo G, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haan, David, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Hamilton, Mark P, Han, Leng, Hanna, George B, Hansmann, Martin, Haradhvala, Nicholas J, Harismendy, Olivier, Harliwong, Ivon, Harmanci, Arif O, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hess, Julian M, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hobolth, Asger, Hodzic, Ermin, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Chen, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hornshøj, Henrik, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, 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Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.
Published: 2023
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10. Combined burden and functional impact tests for cancer driver discovery using DriverPower

Author: Shuai, Shimin, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Barenboim, Jonathan, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reimand, Jüri, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, Uusküla-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven PC, Wadelius, Claes, Wadi, Lina, Wang, Jiayin, Warrell, Jonathan, Waszak, Sebastian M, Weischenfeldt, Joachim, Wheeler, David A, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, von Mering, Christian, Gallinger, Steven, Aaltonen, Lauri A, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, 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Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshpande, Vikram, Deshwar, Amit G, Desmedt, Christine, Dhalla, Noreen, Dhani, Neesha C, Dhir, Rajiv, DiBiase, Anthony, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, 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Stephen H, Kazanov, Marat D, Keays, Maria, Kebebew, Electron, Kefford, Richard F, Kench, James G, Kennedy, Catherine J, Kerssemakers, Jules NA, Khoo, David, Khoo, Vincent, Khuntikeo, Narong, Kilpinen, Helena, Kim, Hark Kyun, Kim, Hyung-Lae, Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jihoon, King, Tari A, Klapper, Wolfram, Kleinheinz, Kortine, Klimczak, Leszek J, Knappskog, Stian, Kneba, Michael, Knoppers, Bartha M, Koh, Youngil, Komura, Daisuke, Komura, Mitsuhiro, Kong, Gu, Kool, Marcel, Korchina, Viktoriya, Korshunov, Andrey, Koscher, Michael, Koster, Roelof, Kote-Jarai, Zsofia, Koures, Antonios, Kovacevic, Milena, Kremeyer, Barbara, Kretzmer, Helene, Kreuz, Markus, Krishnamurthy, Savitri, Kube, Dieter, Kumar, Kiran, Kumar, Pardeep, Kumar, Yogesh, Kundra, Ritika, Kübler, Kirsten, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H, Laird, Peter W, Lakhani, Sunil R, Lalansingh, Christopher M, Lalonde, Emilie, Lamaze, Fabien C, Lambert, Adam, Lander, Eric, Landgraf, Pablo, Landoni, Luca, Langerød, Anita, Larsimont, Denis, Lathrop, Mark, Lau, Loretta MS, Lawerenz, Chris, Lawlor, Rita T, Lazar, Alexander J, Lazic, Ana Mijalkovic, Le, Xuan, Lee, Darlene, Lee, Eunjung Alice, Lee, Hee Jin, Lee, Jake June-Koo, Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael, Lee-Six, Henry, Lehrach, Hans, Lenze, Dido, Leonard, Conrad R, Leongamornlert, Daniel A, Leshchiner, Ignaty, Letourneau, Louis, Letunic, Ivica, Levine, Douglas A, Lewis, Lora, Ley, Tim, Li, Chang, Li, Constance H, Li, Haiyan Irene, Li, Jun, Li, Lin, Li, Siliang, Li, Xiaobo, Li, Xinyue, Li, Yilong, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Linehan, WM, Lingjærde, Ole Christian, Liu, Dongbing, Liu, Fei-Fei Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, Livitz, Dimitri, Livni, Naomi, Loeffler, Markus, Long, Georgina V, Lopez-Guillermo, Armando, Louis, David N, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lynch, Andy G, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, Macintyre, Geoff, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowetz, Florian, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin, Sancha, Martin-Subero, Jose I, Mashl, R Jay, Massie, Charlie E, Matthew, Thomas J, Matthews, Lucy, Mayer, Erik, Mayes, Simon, Mayo, Michael, Mbabaali, Faridah, McCune, Karen, McDermott, Ultan, McLellan, Michael D, McPherson, John D, McPherson, John R, McPherson, Treasa A, Meier, Samuel R, Meng, Alice, Meng, Shaowu, Menzies, Andrew, Merrett, Neil D, Merson, Sue, Meyerson, Matthew, Mieczkowski, Piotr A, Mihaiescu, George L, Mijalkovic, Sanja, Mikkelsen, Tom, Milella, Michele, Mileshkin, Linda, Miller, Christopher A, Miller, David K, Miller, Jessica K, Mills, Gordon B, Milovanovic, Ana, Minner, Sarah, Miotto, Marco, Arnau, Gisela Mir, Mirabello, Lisa, Mitchell, Chris, Mitchell, Thomas J, Miyano, Satoru, Miyoshi, Naoki, Mizuno, Shinichi, Molnár-Gábor, Fruzsina, Moore, Malcolm J, Moore, Richard A, Morganella, Sandro, Morris, Quaid D, Morrison, Carl, Mose, Lisle E, Moser, Catherine D, Mungall, Andrew J, Mungall, Karen, Musgrove, Elizabeth A, Mustonen, Ville, Mutch, David, Muyas, Francesc, Muzny, Donna M, Muñoz, Alfonso, Myers, Jerome, Myklebost, Ola, Möller, Peter, Nagae, Genta, Nagrial, Adnan M, Nahal-Bose, Hardeep K, Nakagama, Hitoshi, Nakamura, Hiromi, Nakamura, Toru, Nakano, Kaoru, Nandi, Tannistha, Nangalia, Jyoti, Nastic, Mia, Navarro, Arcadi, Navarro, Fabio CP, Neal, David E, Nettekoven, Gerd, Newell, Felicity, Newhouse, Steven J, Newton, Yulia, Ng, Alvin Wei Tian, Ng, Anthony, Nicholson, Jonathan, Nicol, David, Nie, Yongzhan, Nielsen, G Petur, Nik-Zainal, Serena, Noble, Michael S, Nones, Katia, Northcott, Paul A, Notta, Faiyaz, O’Connor, Brian D, O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A, Ojesina, Akinyemi I, Ojima, Hidenori, Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ossowski, Stephan, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Peter J, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pearson, John V, Pedamallu, Chandra Sekhar, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, Prinz, Manuel, Pritchard, Antonia L, Prokopec, Stephenie D, Provenzano, Elena, Puente, Xose S, Puig, Sonia, Puiggròs, Montserrat, Pupo, Gulietta M, Purdie, Colin A, Quinn, Michael C, Rabionet, Raquel, Rader, Janet S, Radlwimmer, Bernhard, Radovic, Petar, Raeder, Benjamin, Raine, Keiran M, Ramakrishna, Manasa, Ramakrishnan, Kamna, Ramalingam, Suresh, Rathmell, W Kimryn, Rausch, Tobias, Reifenberger, Guido, Reis-Filho, Jorge, Reuter, Victor, Reynolds, Sheila M, Riazalhosseini, Yasser, Richardson, Andrea L, Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Rippe, Karsten, Roach, Jeffrey, Roberts, Lewis R, Roberts, Nicola D, Roberts, Steven A, Robertson, A Gordon, Robertson, Alan J, Rodriguez, Javier Bartolomé, Rodriguez-Martin, Bernardo, Rodríguez-González, F Germán, Roehrl, Michael HA, Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C, Rosenwald, Andreas, Rowe, Edward W, Royo, Romina, Rozen, Steven G, Rubanova, Yulia, Rudneva, Vasilisa A, Rusev, Borislav C, Ruzzenente, Andrea, Rätsch, Gunnar, Sabarinathan, Radhakrishnan, Sabelnykova, Veronica Y, Sadeghi, Sara, Saini, Natalie, Saito-Adachi, Mihoko, Salcedo, Adriana, Salgado, Roberto, Sallari, Richard, Saller, Charles, Salvia, Roberto, Sam, Michelle, Samra, Jaswinder S, Sanchez-Vega, Francisco, Sanders, Grant, Sarin, Rajiv, Sarrafi, Iman, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn PM, Scardoni, Maria, Scarlett, Christopher J, Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E, Schilhabel, Markus B, Schlesner, Matthias, Schlomm, Thorsten, Schmidt, Heather K, Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schwarz, Roland F, Scolyer, Richard A, Scott, David, Scully, Ralph, Seethala, Raja, Segre, Ayellet V, Selander, Iris, Semple, Colin A, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shelton, Troy, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shringarpure, Suyash S, Shriver, Craig, Siebert, Reiner, Sieuwerts, Anieta M, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, MC Tubio, Jose, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Villasante, Izar, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M, Waddell, Nicola, Wagener, Rabea, Wala, Jeremiah A, Wang, Jian, Wang, Linghua, Wang, Qi, Wang, Wenyi, Wang, Yumeng, Wang, Zhining, Waring, Paul M, Warnatz, Hans-Jörg, Warren, Anne Y, Wedge, David C, Weichenhan, Dieter, Weinberger, Paul, Weinstein, John N, Weisenberger, Daniel J, Welch, Ian, Wendl, Michael C, Werner, Johannes, Whalley, Justin P, Whitaker, Hayley C, Wigle, Dennis, Wilkerson, Matthew D, Williams, Ashley, Wilmott, James S, Wilson, Gavin W, Wilson, Julie M, Wilson, Richard K, Winterhoff, Boris, Wintersinger, Jeffrey A, Wiznerowicz, Maciej, Wolf, Stephan, Wong, Bernice H, Wong, Tina, Wong, Winghing, Woo, Youngchoon, Wood, Scott, Wouters, Bradly G, Wright, Adam J, Wright, Derek W, Wright, Mark H, Wu, Chin-Lee, Wu, Dai-Ying, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Zhenggang, Xi, Liu, Xia, Tian, Xiang, Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Junjun, Zhang, Xiuqing, Zhang, Zemin, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, and Veer, L van’t
Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.
Published: 2023
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11. Integrative pathway enrichment analysis of multivariate omics data

Author: Paczkowska, Marta, Barenboim, Jonathan, Sintupisut, Nardnisa, Fox, Natalie S, Zhu, Helen, Abd-Rabbo, Diala, Mee, Miles W, Boutros, Paul C, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Gonzalez-Perez, Abel, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pich, Oriol, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sabarinathan, Radhakrishnan, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, 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Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Junjun, Zhang, Xiuqing, Zhang, Zemin, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, and Veer, L van’t
Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
Published: 2023
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12. Pathway and network analysis of more than 2500 whole cancer genomes

Author: Reyna, Matthew A, Haan, David, Paczkowska, Marta, Verbeke, Lieven PC, Vazquez, Miguel, Kahraman, Abdullah, Pulido-Tamayo, Sergio, Barenboim, Jonathan, Wadi, Lina, Dhingra, Priyanka, Shrestha, Raunak, Getz, Gad, Lawrence, Michael S, Pedersen, Jakob Skou, Rubin, Mark A, Wheeler, David A, Brunak, Søren, Izarzugaza, Jose MG, Khurana, Ekta, Marchal, Kathleen, von Mering, Christian, Sahinalp, S Cenk, Valencia, Alfonso, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Busanovich, John, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Guo, Qianyun, Gut, Ivo G, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, 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Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
Published: 2023
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13. Divergent mutational processes distinguish hypoxic and normoxic tumours

Author: Bhandari, Vinayak, Li, Constance H, Bristow, Robert G, Boutros, Paul C, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhosle, Shriram G, Biankin, Andrew V, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, 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Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Junjun, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
Published: 2023
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14. Genomic footprints of activated telomere maintenance mechanisms in cancer

Author: Sieverling, Lina, Hong, Chen, Koser, Sandra D, Ginsbach, Philip, Kleinheinz, Kortine, Hutter, Barbara, Braun, Delia M, Cortés-Ciriano, Isidro, Xi, Ruibin, Kabbe, Rolf, Park, Peter J, Eils, Roland, Schlesner, Matthias, Akdemir, Kadir C, Alvarez, Eva G, Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C, Bowtell, David DL, Brors, Benedikt, Burns, Kathleen H, Campbell, Peter J, Chan, Kin, Chen, Ken, Dueso-Barroso, Ana, Dunford, Andrew J, Edwards, Paul A, Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W, Gerstein, Mark, Gordenin, Dmitry A, Haan, David, Haber, James E, Hess, Julian M, Imielinski, Marcin, Jones, David TW, Ju, Young Seok, Kazanov, Marat D, Klimczak, Leszek J, Koh, Youngil, Korbel, Jan O, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Li, Yilong, Lynch, Andy G, Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Meyerson, Matthew, Miyano, Satoru, Nakagawa, Hidewaki, Navarro, Fabio CP, Ossowski, Stephan, Pearson, John V, Puiggròs, Montserrat, Rippe, Karsten, Roberts, Nicola D, Roberts, Steven A, Rodriguez-Martin, Bernardo, Schumacher, Steven E, Scully, Ralph, Shackleton, Mark, Sidiropoulos, Nikos, Stewart, Chip, Torrents, David, MC Tubio, Jose, Villasante, Izar, Waddell, Nicola, Wala, Jeremiah A, Weischenfeldt, Joachim, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zamora, Jorge, Zhang, Cheng-Zhong, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, 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Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Eyfjord, Jorunn E, Faltas, Bishoy M, Fan, Daiming, Fan, Yu, Faquin, William C, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Field, Matthew A, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Fonseca, Nuno A, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Friedman, William, Frigola, Joan, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey 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Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imoto, Seiya, Isaacs, William B, Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose MG, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Jiao, Wei, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Johnson, Rory, Johnson, Todd A, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, Nic, Jones, 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Michael, Koster, Roelof, Kote-Jarai, Zsofia, Koures, Antonios, Kovacevic, Milena, Kremeyer, Barbara, Kretzmer, Helene, Kreuz, Markus, Krishnamurthy, Savitri, Kube, Dieter, Kumar, Pardeep, Kumar, Sushant, Kumar, Yogesh, Kundra, Ritika, Kübler, Kirsten, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H, Laird, Peter W, Lakhani, Sunil R, Lalansingh, Christopher M, Lalonde, Emilie, Lamaze, Fabien C, Lambert, Adam, Lander, Eric, Landgraf, Pablo, Landoni, Luca, Langerød, Anita, Lanzós, Andrés, Larsimont, Denis, Larsson, Erik, Lathrop, Mark, Lau, Loretta MS, Lawerenz, Chris, Lawlor, Rita T, Lawrence, Michael S, Lazar, Alexander J, Lazic, Ana Mijalkovic, Le, Xuan, Lee, Darlene, Lee, Donghoon, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael, Lee-Six, Henry, Lehmann, Kjong-Van, Lehrach, Hans, Lenze, Dido, Leonard, Conrad R, Leongamornlert, Daniel A, Leshchiner, Ignaty, Letourneau, Louis, Letunic, Ivica, Levine, Douglas A, Lewis, Lora, Ley, Tim, Li, Chang, Li, Constance H, Li, Haiyan Irene, Li, Jun, Li, Lin, Li, Shantao, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Lin, Ziao, Linehan, WM, Lingjærde, Ole Christian, Liu, Dongbing, Liu, Eric Minwei, Liu, Fei-Fei Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, Livitz, Dimitri, Livni, Naomi, Lochovsky, Lucas, Loeffler, Markus, Long, Georgina V, Lopez-Guillermo, Armando, Lou, Shaoke, Louis, David N, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, Madsen, Tobias, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchal, Kathleen, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin, Sancha, Martin-Subero, Jose I, Maruvka, Yosef E, Mashl, R Jay, Massie, Charlie E, Matthew, Thomas J, Matthews, Lucy, Mayer, Erik, Mayes, Simon, Mayo, Michael, Mbabaali, Faridah, McCune, Karen, McDermott, Ultan, McGillivray, Patrick D, McLellan, Michael D, McPherson, John D, McPherson, John R, McPherson, Treasa A, Meier, Samuel R, Meng, Alice, Meng, Shaowu, Menzies, Andrew, Merrett, Neil D, Merson, Sue, Meyerson, William, Mieczkowski, Piotr A, Mihaiescu, George L, Mijalkovic, Sanja, Mikkelsen, Tom, Milella, Michele, Mileshkin, Linda, Miller, Christopher A, Miller, David K, Miller, Jessica K, Mills, Gordon B, Milovanovic, Ana, Minner, Sarah, Miotto, Marco, Arnau, Gisela Mir, Mirabello, Lisa, Mitchell, Chris, Mitchell, Thomas J, Miyoshi, Naoki, Mizuno, Shinichi, Molnár-Gábor, Fruzsina, Moore, Malcolm J, Moore, Richard A, Morganella, Sandro, Morris, Quaid D, Morrison, Carl, Mose, Lisle E, Moser, Catherine D, Muiños, Ferran, Mularoni, Loris, Mungall, Andrew J, Mungall, Karen, Musgrove, Elizabeth A, Mustonen, Ville, Mutch, David, Muyas, Francesc, Muzny, Donna M, Muñoz, Alfonso, Myers, Jerome, Myklebost, Ola, Möller, Peter, Nagae, Genta, Nagrial, Adnan M, Nahal-Bose, Hardeep K, Nakagama, Hitoshi, Nakamura, Hiromi, Nakamura, Toru, Nakano, Kaoru, Nandi, Tannistha, Nangalia, Jyoti, Nastic, Mia, Navarro, Arcadi, Neal, David E, Nettekoven, Gerd, Newell, Felicity, Newhouse, Steven J, Newton, Yulia, Ng, Alvin Wei Tian, Ng, Anthony, Nicholson, Jonathan, Nicol, David, Nie, Yongzhan, Nielsen, G Petur, Nielsen, Morten Muhlig, Nik-Zainal, Serena, Noble, Michael S, Nones, Katia, Northcott, Paul A, Notta, Faiyaz, O’Connor, Brian D, O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A, Ojesina, Akinyemi I, Ojima, Hidenori, Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, 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Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shapira, Ofer, Shelton, Troy, Shen, Ciyue, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shrestha, Raunak, Shringarpure, Suyash S, Shriver, Craig, Shuai, Shimin, Siebert, Reiner, Sieuwerts, Anieta M, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sinnott-Armstrong, Nasa, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stein, Lincoln D, Stenhouse, Alasdair, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stuart, Joshua M, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tamborero, David, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tiao, Grace, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, Tsunoda, Tatsuhiko, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Umer, Husen M, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Uusküla-Reimand, Liis, Valencia, Alfonso, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vazquez, Miguel, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Verbeke, Lieven PC, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M, Wadelius, Claes, Wadi, Lina, Wagener, Rabea, Wang, Jian, Wang, Jiayin, Wang, Linghua, Wang, Qi, Wang, Wenyi, Wang, Yumeng, Wang, Zhining, Waring, Paul M, Warnatz, Hans-Jörg, Warrell, Jonathan, Warren, Anne Y, Waszak, Sebastian M, Wedge, David C, Weichenhan, Dieter, Weinberger, Paul, Weinstein, John N, Weisenberger, Daniel J, Welch, Ian, Wendl, Michael C, Werner, Johannes, Whalley, Justin P, Wheeler, David A, Whitaker, Hayley C, Wigle, Dennis, Wilkerson, Matthew D, Williams, Ashley, Wilmott, James S, Wilson, Gavin W, Wilson, Julie M, Wilson, Richard K, Winterhoff, Boris, Wintersinger, Jeffrey A, Wiznerowicz, Maciej, Wolf, Stephan, Wong, Bernice H, Wong, Tina, Wong, Winghing, Woo, Youngchoon, Wood, Scott, Wouters, Bradly G, Wright, Adam J, Wright, Derek W, Wright, Mark H, Wu, Chin-Lee, Wu, Dai-Ying, Wu, Guanming, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Zhenggang, Xi, Liu, Xia, Tian, Xiang, Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Junjun, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
Published: 2023
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15. Clinical and biological implications of driver mutations in myelodysplastic syndromes

Author: Papaemmanuil, Elli, Gerstung, Moritz, Malcovati, Luca, Tauro, Sudhir, Gundem, Gunes, Van Loo, Peter, Yoon, Chris J., Ellis, Peter, Wedge, David C., Pellagatti, Andrea, Shlien, Adam, Groves, Michael John, Forbes, Simon A., Raine, Keiran, Hinton, Jon, Mudie, Laura J., McLaren, Stuart, Hardy, Claire, Latimer, Calli, Della Porta, Matteo G., O'Meara, Sarah, Ambaglio, Ilaria, Galli, Anna, Butler, Adam P., Walldin, Gunilla, Teague, Jon W., Quek, Lynn, Sternberg, Alex, Gambacorti-Passerini, Carlo, Cross, Nicholas C.P., Green, Anthony R., Boultwood, Jacqueline, Vyas, Paresh, Hellstrom-Lindberg, Eva, Bowen, David, Cazzola, Mario, Stratton, Michael R., and Campbell, Peter J.
Published: 2013
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16. COSMIC: exploring the worldʼs knowledge of somatic mutations in human cancer

Author: Forbes, Simon A., Beare, David, Gunasekaran, Prasad, Leung, Kenric, Bindal, Nidhi, Boutselakis, Harry, Ding, Minjie, Bamford, Sally, Cole, Charlotte, Ward, Sari, Kok, Chai Yin, Jia, Mingming, De, Tisham, Teague, Jon W., Stratton, Michael R., McDermott, Ultan, and Campbell, Peter J.
Published: 2015
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17. Whole exome sequencing of adenoid cystic carcinoma

Author: Stephens, Philip J., Davies, Helen R., Mitani, Yoshitsugu, Van Loo, Peter, Shlien, Adam, Tarpey, Patrick S., Papaemmanuil, Elli, Cheverton, Angela, Bignell, Graham R., Butler, Adam P., Gamble, John, Gamble, Stephen, Hardy, Claire, Hinton, Jonathan, Jia, Mingming, Jayakumar, Alagu, Jones, David, Latimer, Calli, McLaren, Stuart, McBride, David J., Menzies, Andrew, Mudie, Laura, Maddison, Mark, Raine, Keiran, Nik-Zainal, Serena, O'Meara, Sarah, Teague, Jon W., Varela, Ignacio, Wedge, David C., Whitmore, Ian, Lippman, Scott M., McDermott, Ultan, Stratton, Michael R., Campbell, Peter J., Naggar, Adel K., and Futreal, P. Andrew
Subjects: Nucleotide sequencing -- Research, DNA sequencing -- Research, Carcinoma -- Physiological aspects -- Genetic aspects, Cancer -- Genetic aspects -- Physiological aspects, Health care industry
Abstract: Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of [...]
Published: 2013
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18. The patterns and dynamics of genomic instability in metastatic pancreatic cancer

Author: Campbell, Peter J., Yachida, Shinichi, Mudie, Laura J., Stephens, Philip J., Pleasance, Erin D., Stebbings, Lucy A., Morsberger, Laura A., Latimer, Calli, McLaren, Stuart, Lin, Meng-Lay, McBride, David J., Varela, Ignacio, Nik-Zainal, Serena A., Leroy, Catherine, Jia, Mingming, Menzies, Andrew, Butler, Adam P., Teague, Jon W., Griffin, Constance A., Burton, John, Swerdlow, Harold, Quail, Michael A., Stratton, Michael R., Iacobuzio-Donahue, Christine, and Futreal, P. Andrew
Subjects: Metastasis -- Research -- Genetic aspects -- Patient outcomes, Cancer -- Genetic aspects, Pancreatic cancer -- Genetic aspects -- Patient outcomes -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97-98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations (1-5), but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours (6,7), including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites (7), and how the tumour disseminates. Here we harness advances in DNA sequencing (8-12) to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2-M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection., We performed massively parallel paired-end sequencing to identify somatically acquired genomic rearrangements in 13 patients with pancreatic adenocarcinoma (Supplementary Table 1). For each sample, we generated 50-150-million paired sequences of [...]
Published: 2010
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19. Mutational signatures in esophageal squamous cell carcinoma from eight countries of varying incidence

Author: Moody, Sarah, primary, Senkin, Sergey, additional, Islam, S M Ashiqul, additional, Wang, Jingwei, additional, Nasrollahzadeh, Dariush, additional, Penha, Ricardo Cortez Cardoso, additional, Fitzgerald, Stephen, additional, Bergstrom, Erik N, additional, Atkins, Joshua, additional, He, Yudou, additional, Khandekar, Azhar, additional, Smith-Byrne, Karl, additional, Carreira, Christine, additional, Gaborieau, Valerie, additional, Latimer, Calli, additional, Thomas, Emily, additional, Abnizova, Irina, additional, Bucciarelli, Pauline E, additional, Jones, David, additional, Teague, Jon W, additional, Abedi-Ardekani, Behnoush, additional, Serra, Stefano, additional, Scoazec, Jean-Yves, additional, Saffar, Hiva, additional, Azmoudeh-Ardelan, Farid, additional, Sotoudeh, Masoud, additional, Nikmanesh, Arash, additional, Eden, Michael, additional, Richman, Paul, additional, Campos, Lia S, additional, Fitzgerald, Rebecca C, additional, Ribeiro, Luis Felipe, additional, Dzamalala, Charles, additional, Mmbaga, Blandina Theophil, additional, Shibata, Tatsuhiro, additional, Menya, Diana, additional, Goldstein, Alisa M, additional, Hu, Nan, additional, Malekzadeh, Reza, additional, Fazel, Abdolreza, additional, McCormack, Valerie, additional, McKay, James, additional, Perdomo, Sandra, additional, Scelo, Ghislaine, additional, Chanudet, Estelle, additional, Humphreys, Laura, additional, Alexandrov, Ludmil B, additional, Brennan, Paul, additional, and Stratton, Michael R, additional
Published: 2021
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20. Mutational processes molding the genomes of 21 breast cancers

Author: Nik-Zainal, Serena, Alexandrov, Ludmil B, Wedge, David C, Van Loo, Peter, Greenman, Christopher D, Raine, Keiran, Jones, David, Hinton, Jonathan, Marshall, John, Stebbings, Lucy A, Menzies, Andrew, Martin, Sancha, Leung, Kenric, Chen, Lina, Leroy, Catherine, Ramakrishna, Manasa, Rance, Richard, Lau, King Wai, Mudie, Laura J, Varela, Ignacio, McBride, David J, Bignell, Graham R, Cooke, Susanna L, Shlien, Adam, Gamble, John, Whitmore, Ian, Maddison, Mark, Tarpey, Patrick S, Davies, Helen R, Papaemmanuil, Elli, Stephens, Philip J, McLaren, Stuart, Butler, Adam P, Teague, Jon W, Jönsson, Göran, Garber, Judy E, Silver, Daniel, Miron, Penelope, Fatima, Aquila, Boyault, Sandrine, Langerød, Anita, Tutt, Andrew, Martens, John WM, Aparicio, Samuel AJR, Borg, Åke, Salomon, Anne Vincent, Thomas, Gilles, Børresen-Dale, Anne-Lise, Richardson, Andrea L, Neuberger, Michael S, Futreal, P Andrew, Campbell, Peter J, Stratton, Michael R, Breast Cancer Working Group of the International Cancer Genome Consortium, Nik-Zainal Abidin, Serena [0000-0001-5054-1727], and Apollo - University of Cambridge Repository
Subjects: BRCA2 Protein, APOBEC-1 Deaminase, Cytidine Deaminase, DNA Mutational Analysis, Mutation, Genes, BRCA1, High-Throughput Nucleotide Sequencing, Humans, Breast Neoplasms, Female, Genome-Wide Association Study
Abstract: All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis," was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed.
Published: 2020
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21. The life history of 21 breast cancers

Author: Nik-Zainal, Serena, Van Loo, Peter, Wedge, David C, Alexandrov, Ludmil B, Greenman, Christopher D, Lau, King Wai, Raine, Keiran, Jones, David, Marshall, John, Ramakrishna, Manasa, Shlien, Adam, Cooke, Susanna L, Hinton, Jonathan, Menzies, Andrew, Stebbings, Lucy A, Leroy, Catherine, Jia, Mingming, Rance, Richard, Mudie, Laura J, Gamble, Stephen J, Stephens, Philip J, McLaren, Stuart, Tarpey, Patrick S, Papaemmanuil, Elli, Davies, Helen R, Varela, Ignacio, McBride, David J, Bignell, Graham R, Leung, Kenric, Butler, Adam P, Teague, Jon W, Martin, Sancha, Jönsson, Goran, Mariani, Odette, Boyault, Sandrine, Miron, Penelope, Fatima, Aquila, Langerød, Anita, Aparicio, Samuel AJR, Tutt, Andrew, Sieuwerts, Anieta M, Borg, Åke, Thomas, Gilles, Salomon, Anne Vincent, Richardson, Andrea L, Børresen-Dale, Anne-Lise, Futreal, P Andrew, Stratton, Michael R, Campbell, Peter J, Breast Cancer Working Group of the International Cancer Genome Consortium, Nik-Zainal Abidin, Serena [0000-0001-5054-1727], and Apollo - University of Cambridge Repository
Subjects: Chromosome Aberrations, Clonal Evolution, Cell Transformation, Neoplastic, Mutation, Humans, Point Mutation, Breast Neoplasms, Female, Algorithms
Abstract: Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.
Published: 2020
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22. Pan-cancer analysis of whole genomes

Author: Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O'Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon, I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet, V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortes-Ciriano, Isidro, Urban, Lara, Park, Peter, Pitkaenen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Ratsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnar-Gabor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Pineiro-Yanez, Elena, Munoz, Alfonso, Petryszak, Robert, Fullgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jaeger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggros, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Juri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, Andre, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioglu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurelien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi, I, Pan-Hammarstrom, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Goke, Jonathan, Zhang, Zemin, Brooks, Angela N., Martincorena, Inigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshoj, Henrik, Deu-Pons, Jordi, Muinos, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Huebschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Soren, Fita, Joana Carlevaro, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Rory, Juul, Randi Istrup, Kim, Jaegil, Kim, Jong K., Komorowski, Jan, Lanzos, Andres, Larsson, Erik, Lee, Donghoon, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Fundichely, Alexander Martinez, McGillivray, Patrick D., Meyerson, William, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes Salazar, Iker, Reyna, Matthew A., Rubin, Mark A., Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Tsunoda, Tatsuhiko, Umer, Husen M., Uuskula-Reimand, Liis, Verbeke, Lieven P. C., Wadelius, Claes, Wadi, Lina, Warrell, Jonathan, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, Lawrence, Michael S., Raphael, Benjamin J., Bailey, Peter J., Craft, David, Goldman, Mary J., Aburatani, Hiroyuki, Binder, Hans, Dinh, Huy Q., Heath, Simon C., Hoffmann, Steve, Imbusch, Charles David, Kretzmer, Helene, Laird, Peter W., Martin-Subero, Jose, I, Nagae, Genta, Shen, Hui, Wang, Qi, Weichenhan, Dieter, Zhou, Wanding, Berman, Benjamin P., Brors, Benedikt, Plass, Christoph, Akdemir, Kadir C., Bowtell, David D. L., Burns, Kathleen H., Busanovich, John, Chan, Kin, Dueso-Barroso, Ana, Edwards, Paul A., Etemadmoghadam, Dariush, Haber, James E., Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Koh, Youngil, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Navarro, Fabio C. P., Pearson, John, V, Rippe, Karsten, Scully, Ralph, Villasante, Izar, Waddell, Nicola, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zhang, Cheng-Zhong, Bergstrom, Erik N., Boot, Arnoud, Covington, Kyle, Fujimoto, Akihiro, Huang, Mi Ni, Islam, S. M. Ashiqul, McPherson, John R., Morganella, Sandro, Mustonen, Ville, Ng, Alvin Wei Tian, Prokopec, Stephenie D., Vazquez-Garcia, Ignacio, Wu, Yang, Yousif, Fouad, Yu, Willie, Rozen, Steven G., Rudneva, Vasilisa A., Shringarpure, Suyash S., Turner, Daniel J., Xia, Tian, Atwal, Gurnit, Chang, David K., Cooke, Susanna L., Faltas, Bishoy M., Haider, Syed, Kaiser, Vera B., Karlic, Rosa, Kato, Mamoru, Kubler, Kirsten, Margolin, Adam, Martin, Sancha, Nik-Zainal, Serena, P'ng, Christine, Semple, Colin A., Smith, Jaclyn, Sun, Ren X., Thai, Kevin, Wright, Derek W., Yuan, Ke, Biankin, Andrew, V, Garraway, Levi, Grimmond, Sean M., Adams, David J., Anur, Pavana, Cao, Shaolong, Christie, Elizabeth L., Cmero, Marek, Cun, Yupeng, Dawson, Kevin J., Dentro, Stefan C., Deshwar, Amit G., Donmez, Nilgun, Drews, Ruben M., Gerstung, Moritz, Ha, Gavin, Haase, Kerstin, Jerman, Lara, Ji, Yuan, Jolly, Clemency, Lee, Juhee, Lee-Six, Henry, Malikic, Salem, Mitchell, Thomas J., Morris, Quaid D., Oesper, Layla, Peifer, Martin, Peto, Myron, Rosebrock, Daniel, Rubanova, Yulia, Salcedo, Adriana, Sengupta, Subhajit, Shi, Ruian, Shin, Seung Jun, Spiro, Oliver, Vembu, Shankar, Wintersinger, Jeffrey A., Yang, Tsun-Po, Yu, Kaixian, Zhu, Hongtu, Spellman, Paul T., Weinstein, John N., Chen, Yiwen, Fujita, Masashi, Han, Leng, Hasegawa, Takanori, Komura, Mitsuhiro, Li, Jun, Mizuno, Shinichi, Shimizu, Eigo, Wang, Yumeng, Xu, Yanxun, Yamaguchi, Rui, Yang, Fan, Yang, Yang, Yoon, Christopher J., Yuan, Yuan, Liang, Han, Alawi, Malik, Borozan, Ivan, Brewer, Daniel S., Cooper, Colin S., Desai, Nikita, Grundhoff, Adam, Iskar, Murat, Su, Xiaoping, Zapatka, Marc, Lichter, Peter, Alsop, Kathryn, Bruxner, Timothy J. C., Christ, Angelika N., Cordner, Stephen M., Cowin, Prue A., Drapkin, Ronny, Fereday, Sian, George, Joshy, Hamilton, Anne, Holmes, Oliver, Hung, Jillian A., Kassahn, Karin S., Kazakoff, Stephen H., Kennedy, Catherine J., Leonard, Conrad R., Mileshkin, Linda, Miller, David K., Arnau, Gisela Mir, Mitchell, Chris, Newell, Felicity, Nones, Katia, Patch, Ann-Marie, Quinn, Michael C., Taylor, Darrin F., Thorne, Heather, Traficante, Nadia, Vedururu, Ravikiran, Waddell, Nick M., Waring, Paul M., Wood, Scott, Xu, Qinying, DeFazio, Anna, Anderson, Matthew J., Antonello, Davide, Barbour, Andrew P., Bassi, Claudio, Bersani, Samantha, Cataldo, Ivana, Chantrill, Lorraine A., Chiew, Yoke-Eng, Chou, Angela, Cingarlini, Sara, Cloonan, Nicole, Corbo, Vincenzo, Davi, Maria Vittoria, Duthie, Fraser R., Gill, Anthony J., Graham, Janet S., Harliwong, Ivon, Jamieson, Nigel B., Johns, Amber L., Kench, James G., Landoni, Luca, Lawlor, Rita T., Mafficini, Andrea, Merrett, Neil D., Miotto, Marco, Musgrove, Elizabeth A., Nagrial, Adnan M., Oien, Karin A., Pajic, Marina, Pinese, Mark, Robertson, Alan J., Rooman, Ilse, Rusev, Borislav C., Samra, Jaswinder S., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Sereni, Elisabetta, Sikora, Katarzyna O., Simbolo, Michele, Taschuk, Morgan L., Toon, Christopher W., Vicentini, Caterina, Wu, Jianmin, Zeps, Nikolajs, Behren, Andreas, Burke, Hazel, Cebon, Jonathan, Dagg, Rebecca A., De Paoli-Iseppi, Ricardo, Dutton-Regester, Ken, Field, Matthew A., Fitzgerald, Anna, Hersey, Peter, Jakrot, Valerie, Johansson, Peter A., Kakavand, Hojabr, Kefford, Richard F., Lau, Loretta M. S., Long, Georgina, V, Pickett, Hilda A., Pritchard, Antonia L., Pupo, Gulietta M., Saw, Robyn P. M., Schramm, Sarah-Jane, Shang, Catherine A., Shang, Ping, Spillane, Andrew J., Stretch, Jonathan R., Tembe, Varsha, Thompson, John F., Vilain, Ricardo E., Wilmott, James S., Yang, Jean Y., Hayward, Nicholas K., Mann, Graham J., Scolyer, Richard A., Bartlett, John, Bavi, Prashant, Chadwick, Dianne E., Chan-Seng-Yue, Michelle, Cleary, Sean, Connor, Ashton A., Czajka, Karolina, Denroche, Robert E., Dhani, Neesha C., Eagles, Jenna, Gallinger, Steven, Grant, Robert C., Hedley, David, Hollingsworth, Michael A., Jang, Gun Ho, Johns, Jeremy, Kalimuthu, Sangeetha, Liang, Sheng-Ben, Lungu, Ilinca, Luo, Xuemei, Mbabaali, Faridah, McPherson, Treasa A., Miller, Jessica K., Moore, Malcolm J., Notta, Faiyaz, Pasternack, Danielle, Petersen, Gloria M., Roehrl, Michael H. A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jorg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. R., Bhosle, Shriram G., Birney, Ewan, Borg, Ake, Boyault, Sandrine, Brinkman, Arie B., Brock, Jane E., Broeks, Annegien, Borresen-Dale, Anne-Lise, Caldas, Carlos, Chin, Suet-Feung, Davies, Helen, Desmedt, Christine, Dirix, Luc, Dronov, Serge, Ehinger, Anna, Eyfjord, Jorunn E., Fatima, Aquila, Foekens, John A., Futreal, P. Andrew, Garred, Oystein, Giri, Dilip D., Glodzik, Dominik, Grabau, Dorthe, Hilmarsdottir, Holmfridur, Hooijer, Gerrit K., Jacquemier, Jocelyne, Jang, Se Jin, Jonasson, Jon G., Jonkers, Jos, Kim, Hyung-Yong, King, Tari A., Knappskog, Stian, Kong, Gu, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Larsimont, Denis, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Ming Ta Michael, Lingjaerde, Ole Christian, MacGrogan, Gaetan, Martens, John W. M., O'Meara, Sarah, Pauporte, Iris, Pinder, Sarah, Pivot, Xavier, Provenzano, Elena, Purdie, Colin A., Ramakrishna, Manasa, Ramakrishnan, Kamna, Reis-Filho, Jorge, Richardson, Andrea L., Ringner, Markus, Rodriguez, Javier Bartolome, Rodriguez-Gonzalez, F. German, Romieu, Gilles, Salgado, Roberto, Sauer, Torill, Shepherd, Rebecca, Sieuwerts, Anieta M., Simpson, Peter T., Smid, Marcel, Sotiriou, Christos, Span, Paul N., Stefansson, Olafur Andri, Stenhouse, Alasdair, Stunnenberg, Henk G., Sweep, Fred, Tan, Benita Kiat Tee, Thomas, Gilles, Thompson, Alastair M., Tommasi, Stefania, Treilleux, Isabelle, Tutt, Andrew, Ueno, Naoto T., Van Laere, Steven, Van den Eynden, Gert G., Vermeulen, Peter, Viari, Alain, Vincent-Salomon, Anne, Wong, Bernice H., Yates, Lucy, Zou, Xueqing, van Deurzen, Carolien H. M., van de Vijver, Marc J., van't Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica, I, Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Kueppers, Ralf, Lenze, Dido, Loeffler, Markus, Lopez, Cristina, Mantovani-Loeffler, Luisa, Moeller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Truemper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Joerg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sueltmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantu, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, Lopez-Otin, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O'Donovan, Maria, O'Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavare, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barnholtz-Sloan, Jill, Bathe, Oliver F., Baylin, Stephen B., Benz, Christopher, Berchuck, Andrew, Berrios, Mario, Bigner, Darell, Birrer, Michael, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bosenberg, Marcus, Bowlby, Reanne, Boyd, Jeffrey, Broaddus, Russell R., Brock, Malcolm, Brooks, Denise, Bullman, Susan, Caesar-Johnson, Samantha J., Carey, Thomas E., Carlsen, Rebecca, Cerfolio, Robert, Chandan, Vishal S., Chen, Hsiao-Wei, Cherniack, Andrew D., Chien, Jeremy, Cho, Juok, Chuah, Eric, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G., Curley, Erin, Czerniak, Bogdan, Danilova, Ludmila, Davis, Ian J., Defreitas, Timothy, Demchok, John A., Dhalla, Noreen, Dhir, Rajiv, Doddapaneni, HarshaVardhan, El-Naggar, Adel, Felau, Ina, Ferguson, Martin L., Finocchiaro, Gaetano, Fong, Kwun M., Frazer, Scott, Friedman, William, Fronick, Catrina C., Fulton, Lucinda A., Gabriel, Stacey B., Gao, Jianjiong, Gehlenborg, Nils, Gershenwald, Jeffrey E., Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gomez, Carmen, Govindan, Ramaswamy, Hayes, D. Neil, Hegde, Apurva M., Heiman, David, I, Heins, Zachary, Hepperla, Austin J., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Hruban, Ralph H., Hu, Jianhong, Huang, Mei, Huntsman, David, Huse, Jason, Donahue, Christine A. Iacobuzio, Ittmann, Michael, Jayaseelan, Joy C., Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J. M., Juhl, Hartmut, Kang, Koo Jeong, Karlan, Beth, Kasaian, Katayoon, Kebebew, Electron, Kim, Hark Kyun, Korchina, Viktoriya, Kundra, Ritika, Lai, Phillip H., Lander, Eric, Le, Xuan, Lee, Darlene, Levine, Douglas A., Lewis, Lora, Ley, Tim, Li, Haiyan Irene, Lin, Pei, Linehan, W. M., Liu, Fei Fei, Lu, Yiling, Lype, Lisa, Ma, Yussanne, Maglinte, Dennis T., Mardis, Elaine R., Marks, Jeffrey, Marra, Marco A., Matthew, Thomas J., Mayo, Michael, McCune, Karen, Meier, Samuel R., Meng, Shaowu, Mieczkowski, Piotr A., Mikkelsen, Tom, Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morrison, Carl, Mose, Lisle E., Moser, Catherine D., Mungall, Andrew J., Mungall, Karen, Mutch, David, Muzny, Donna M., Myers, Jerome, Newton, Yulia, Noble, Michael S., O'Donnell, Peter, O'Neill, Brian Patrick, Ochoa, Angelica, Park, Joong-Won, Parker, Joel S., Pass, Harvey, Pastore, Alessandro, Pennell, Nathan A., Perou, Charles M., Petrelli, Nicholas, Potapova, Olga, Rader, Janet S., Ramalingam, Suresh, Rathmell, W. Kimryn, Reuter, Victor, Reynolds, Sheila M., Ringel, Matthew, Roach, Jeffrey, Roberts, Lewis R., Robertson, A. Gordon, Sadeghi, Sara, Saller, Charles, Sanchez-Vega, Francisco, Schadendorf, Dirk, Schein, Jacqueline E., Schmidt, Heather K., Schultz, Nikolaus, Seethala, Raja, Senbabaoglu, Yasin, Shelton, Troy, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Shriver, Craig, Signoretti, Sabina, Simons, Janae, V, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J., McCune, Karen Smith, Socci, Nicholas D., Soloway, Matthew G., Sood, Anil K., Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thompson, R. Houston, Thorne, Leigh B., Tsao, Ming, Umbricht, Christopher, Van Den Berg, David J., Van Meir, Erwin G., Veluvolu, Umadevi, Voet, Douglas, Wang, Linghua, Weinberger, Paul, Weisenberger, Daniel J., Wigle, Dennis, Wilkerson, Matthew D., Wilson, Richard K., Winterhoff, Boris, Wiznerowicz, Maciej, Wong, Tina, Wong, Winghing, Xi, Liu, Yau, Christina, Zhang, Hailei, Zhang, Hongxin, Zhang, Jiashan, Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O'Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon, I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet, V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortes-Ciriano, Isidro, Urban, Lara, Park, Peter, Pitkaenen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Ratsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnar-Gabor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Pineiro-Yanez, Elena, Munoz, Alfonso, Petryszak, Robert, Fullgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jaeger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggros, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Juri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, Andre, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioglu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurelien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi, I, Pan-Hammarstrom, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Goke, Jonathan, Zhang, Zemin, Brooks, Angela N., Martincorena, Inigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshoj, Henrik, Deu-Pons, Jordi, Muinos, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Huebschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Soren, Fita, Joana Carlevaro, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Rory, Juul, Randi Istrup, Kim, Jaegil, Kim, Jong K., Komorowski, Jan, Lanzos, Andres, Larsson, Erik, Lee, Donghoon, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Fundichely, Alexander Martinez, McGillivray, Patrick D., Meyerson, William, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes Salazar, Iker, Reyna, Matthew A., Rubin, Mark A., Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Tsunoda, Tatsuhiko, Umer, Husen M., Uuskula-Reimand, Liis, Verbeke, Lieven P. 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A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jorg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. 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M., O'Meara, Sarah, Pauporte, Iris, Pinder, Sarah, Pivot, Xavier, Provenzano, Elena, Purdie, Colin A., Ramakrishna, Manasa, Ramakrishnan, Kamna, Reis-Filho, Jorge, Richardson, Andrea L., Ringner, Markus, Rodriguez, Javier Bartolome, Rodriguez-Gonzalez, F. German, Romieu, Gilles, Salgado, Roberto, Sauer, Torill, Shepherd, Rebecca, Sieuwerts, Anieta M., Simpson, Peter T., Smid, Marcel, Sotiriou, Christos, Span, Paul N., Stefansson, Olafur Andri, Stenhouse, Alasdair, Stunnenberg, Henk G., Sweep, Fred, Tan, Benita Kiat Tee, Thomas, Gilles, Thompson, Alastair M., Tommasi, Stefania, Treilleux, Isabelle, Tutt, Andrew, Ueno, Naoto T., Van Laere, Steven, Van den Eynden, Gert G., Vermeulen, Peter, Viari, Alain, Vincent-Salomon, Anne, Wong, Bernice H., Yates, Lucy, Zou, Xueqing, van Deurzen, Carolien H. M., van de Vijver, Marc J., van't Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica, I, Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Kueppers, Ralf, Lenze, Dido, Loeffler, Markus, Lopez, Cristina, Mantovani-Loeffler, Luisa, Moeller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Truemper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Joerg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sueltmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantu, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, Lopez-Otin, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O'Donovan, Maria, O'Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavare, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. 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Gordon, Sadeghi, Sara, Saller, Charles, Sanchez-Vega, Francisco, Schadendorf, Dirk, Schein, Jacqueline E., Schmidt, Heather K., Schultz, Nikolaus, Seethala, Raja, Senbabaoglu, Yasin, Shelton, Troy, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Shriver, Craig, Signoretti, Sabina, Simons, Janae, V, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J., McCune, Karen Smith, Socci, Nicholas D., Soloway, Matthew G., Sood, Anil K., Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thompson, R. Houston, Thorne, Leigh B., Tsao, Ming, Umbricht, Christopher, Van Den Berg, David J., Van Meir, Erwin G., Veluvolu, Umadevi, Voet, Douglas, Wang, Linghua, Weinberger, Paul, Weisenberger, Daniel J., Wigle, Dennis, Wilkerson, Matthew D., Wilson, Richard K., Winterhoff, Boris, Wiznerowicz, Maciej, Wong, Tina, Wong, Winghing, Xi, Liu, Yau, Christina, Zhang, Hailei, Zhang, Hongxin, and Zhang, Jiashan
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).
Published: 2020

23. Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor

Author: Islam, S M Ashiqul, primary, Díaz-Gay, Marcos, additional, Wu, Yang, additional, Barnes, Mark, additional, Vangara, Raviteja, additional, Bergstrom, Erik N, additional, He, Yudou, additional, Vella, Mike, additional, Wang, Jingwei, additional, Teague, Jon W, additional, Clapham, Peter, additional, Moody, Sarah, additional, Senkin, Sergey, additional, Li, Yun Rose, additional, Riva, Laura, additional, Zhang, Tongwu, additional, Gruber, Andreas J, additional, Steele, Christopher D, additional, Otlu, Burçak, additional, Khandekar, Azhar, additional, Abbasi, Ammal, additional, Humphreys, Laura, additional, Syulyukina, Natalia, additional, Brady, Samuel W, additional, Alexandrov, Boian S, additional, Pillay, Nischalan, additional, Zhang, Jinghui, additional, Adams, David J, additional, Martincorena, Iñigo, additional, Wedge, David C, additional, Landi, Maria Teresa, additional, Brennan, Paul, additional, Stratton, Michael R, additional, Rozen, Steven G, additional, and Alexandrov, Ludmil B, additional
Published: 2020
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24. Signatures of mutational processes in human cancer

Author: Alexandrov, Ludmil B., Nik-Zainal, Serena, Wedge, David C., Aparicio, Samuel A. J. R., Behjati, Sam, Biankin, Andrew V., Bignell, Graham R., Bolli, Niccolò, Borg, Ake, Børresen-Dale, Anne-Lise, Boyault, Sandrine, Burkhardt, Birgit, Butler, Adam P., Caldas, Carlos, Davies, Helen R., Desmedt, Christine, Eils, Roland, Eyfjörd, Jórunn Erla, Foekens, John A., Greaves, Mel, Hosoda, Fumie, Hutter, Barbara, Ilicic, Tomislav, Imbeaud, Sandrine, Imielinsk, Marcin, Jäger, Natalie, Jones, David T. W., Jones, David, Knappskog, Stian, Kool, Marcel, Lakhani, Sunil R., López-Otín, Carlos, Martin, Sancha, Munshi, Nikhil C., Nakamura, Hiromi, Northcott, Paul A., Pajic, Marina, Papaemmanuil, Elli, Paradiso, Angelo, Pearson, John V., Puente, Xose S., Raine, Keiran, Ramakrishna, Manasa, Richardson, Andrea L., Richter, Julia, Rosenstiel, Philip, Schlesner, Matthias, Schumacher, Ton N., Span, Paul N., Teague, Jon W., Totoki, Yasushi, Tutt, Andrew N. J., Valdés-Mas, Rafael, van Buuren, Marit M., van ʼt Veer, Laura, Vincent-Salomon, Anne, Waddell, Nicola, Yates, Lucy R., Zucman-Rossi, Jessica, Futreal, Andrew P., McDermott, Ultan, Lichter, Peter, Meyerson, Matthew, Grimmond, Sean M., Siebert, Reiner, Campo, Elías, Shibata, Tatsuhiro, Pfister, Stefan M., Campbell, Peter J., and Stratton, Michael R.
Published: 2013
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25. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer

Author: Forbes, Simon A., Bindal, Nidhi, Bamford, Sally, Cole, Charlotte, Kok, Chai Yin, Beare, David, Jia, Mingming, Shepherd, Rebecca, Leung, Kenric, Menzies, Andrew, Teague, Jon W., Campbell, Peter J., Stratton, Michael R., and Futreal, P. Andrew
Published: 2011
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26. International network of cancer genome projects

Author: Hudson, Thomas J., Anderson, Warwick, Aretz, Axel, Bell, Cindy, Bernabé, Rosa R., Bhan, M. K., Calvo, Fabien, Eerola, Iiro, Gerhard, Daniela S., Guttmacher, Alan, Guyer, Mark, Hemsley, Fiona M., Jennings, Jennifer L., Kerr, David, Klatt, Peter, Kolar, Patrik, Lane, David P., Laplace, Frank, Nettekoven, Gerd, Ozenberger, Brad, Peterson, Jane, Rao, T. S., Remacle, Jacques, Schafer, Alan J., Shibata, Tatsuhiro, Stratton, Michael R., Watanabe, Koichi, Yuen, Matthew M. F., Cambon-Thomsen, Anne, Dressler, Lynn G., Joly, Yann, Kennedy, Karen L., Parker, Michael J., Romeo-Casabona, Carlos M., Wallace, Susan, Wiesner, Georgia L., Zeps, Nikolajs, Biankin, Andrew V., Chabannon, Christian, de Alava, Enrique, Ferguson, Martin L., Geary, Peter, Hayes, Neil D., Johns, Amber L., Kasprzyk, Arek, Nakagawa, Hidewaki, Piris, Miguel A., van de Vijver, Marc, Aburatani, Hiroyuki, Bayés, Mónica, Bowtell, David D.L., Campbell, Peter J., Hirst, Martin, López-Otín, Carlos, Marra, Marco, Ning, Zemin, Puente, Xose S., Ruan, Yijun, Stunnenberg, Hendrik G., Swerdlow, Harold, Velculescu, Victor E., Xue, Hong H., Yang, Liu, Spellman, Paul T., Bader, Gary D., Boutros, Paul C., Flicek, Paul, Getz, Gad, Guigó, Roderic, Guo, Guangwu, Haussler, David, Hubbard, Tim J., Jiang, Tao, Jones, Steven M., Li, Qibin, López-Bigas, Nuria, Luo, Ruibang, Muthuswamy, Lakshmi, Ouellette, Francis B. F., Pearson, John V., Quesada, Victor, Raphael, Benjamin J., Sander, Chris, Stein, Lincoln D., Stuart, Joshua M., Teague, Jon W., Totoki, Yasushi, Tsunoda, Tatsuhiko, Valencia, Alfonso, Wheeler, David A., Wu, Honglong, Zhao, Shancen, Zhou, Guangyu, Lathrop, Mark, Axton, Myles, Dyke, Stephanie O. M., Gunter, Chris, McPherson, John D., Miller, Linda J., Zhang, Junjun, Haider, Syed A., Wang, Jianxin, Yung, Christina K., Cross, Anthony, Liang, Yong, Gnaneshan, Saravanamuttu, Guberman, Jonathan, Hsu, Jack, Bobrow, Martin, Chalmers, Don R. C., Hasel, Karl W., Kaan, Terry S. H., Knoppers, Bartha M., Lowrance, William W., Masui, Tohru, Nicolás, Pilar, Rial-Sebbag, Emmanuelle, Rodriguez, Laura Lyman, Vergely, Catherine, Grimmond, Sean M., Bowtell, David D. L., Cloonan, Nicole, deFazio, Anna, Eshleman, James R., Etemadmoghadam, Dariush, Gardiner, Brooke A., Kench, James G., Scarpa, Aldo, Sutherland, Robert L., Tempero, Margaret A., Waddell, Nicola J., Wilson, Peter J., Gallinger, Steve, Tsao, Ming-Sound, Shaw, Patricia A., Petersen, Gloria M., Mukhopadhyay, Debabrata, Chin, Lynda, DePinho, Ronald A., Thayer, Sarah, Shazand, Kamran, Beck, Timothy, Sam, Michelle, Timms, Lee, Ballin, Vanessa, Ji, Jiafu, Zhang, Xiuqing, Chen, Feng, Hu, Xueda, Yang, Qi, Tian, Geng, Zhang, Lianhai, Xing, Xiaofang, Li, Xianghong, Zhu, Zhenggang, Yu, Yingyan, Yu, Jun, Yang, Huanming, Tost, Jörg, Brennan, Paul, Holcatova, Ivana, Zaridze, David, Brazma, Alvis, Egevad, Lars, Prokhortchouk, Egor, Banks, Rosamonde Elizabeth, Uhlén, Mathias, Viksna, Juris, Ponten, Fredrik, Skryabin, Konstantin, Futreal, Andrew P., Birney, Ewan, Caldas, Carlos, Reis-Filho, Jorge S., Richardson, Andrea L., Sotiriou, Christos, Birnbaum, Daniel, Blanche, Hélène, Boucher, Pascal, Boyault, Sandrine, Masson-Jacquemier, Jocelyne D., Pauporté, Iris, Pivot, Xavier, Vincent-Salomon, Anne, Tabone, Eric, Theillet, Charles, Treilleux, Isabelle, Bioulac-Sage, Paulette, Clément, Bruno, Decaens, Thomas, Degos, Françoise, Franco, Dominique, Gut, Ivo, Gut, Marta, Heath, Simon, Samuel, Didier, Thomas, Gilles, Zucman-Rossi, Jessica, Eils, Roland, Brors, Benedikt, Korbel, Jan O., Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Pfister, Stefan, Radlwimmer, Bernhard, Reifenberger, Guido, Taylor, Michael D., von Kalle, Christof, Majumder, Partha P., Sarin, Rajiv, Pederzoli, Paolo, Lawlor, Rita T., Delledonne, Massimo, Bardelli, Alberto, Gress, Thomas, Klimstra, David, Zamboni, Giuseppe, Nakamura, Yusuke, Kusuda, Jun, Miyano, Satoru, Kato, Kazuto, Fujimoto, Akihiro, Yoshida, Teruhiko, Campo, Elias, Estivill, Xavier, de Sanjosé, Silvia, Montserrat, Emili, González-Díaz, Marcos, Jares, Pedro, Himmelbaue, Heinz, Bea, Silvia, Aparicio, Samuel, Borg, Ake, Børresen-Dale, Anne-Lise, Foekens, John A., vanʼt Veer, Laura, Easton, Douglas F., Martin, Sancha, Compton, Carolyn C., Lander, Eric S., Penny, Robert, Shaw, Kenna M., Speed, Terence P., Vockley, Joseph G., Lichter, Peter, Barker, Anna D., Burke, Wylie, Collins, Francis S., Green, Anthony R., Hamilton, Stanley R., Kallioniemi, Olli P., Ley, Timothy J., Liu, Edison T., Lu, Youyong, Majumder, Partha, Wainwright, Brandon J., and Wilson, Richard K.
Published: 2010
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27. A small-cell lung cancer genome with complex signatures of tobacco exposure

Author: Pleasance, Erin D., Stephens, Philip J., OʼMeara, Sarah, McBride, David J., Meynert, Alison, Jones, David, Lin, Meng-Lay, Beare, David, Lau, King Wai, Greenman, Chris, Varela, Ignacio, Nik-Zainal, Serena, Davies, Helen R., Ordoñez, Gonzalo R., Mudie, Laura J., Latimer, Calli, Edkins, Sarah, Stebbings, Lucy, Chen, Lina, Jia, Mingming, Leroy, Catherine, Marshall, John, Menzies, Andrew, Butler, Adam, Teague, Jon W., Mangion, Jonathon, Sun, Yongming A., McLaughlin, Stephen F., Peckham, Heather E., Tsung, Eric F., Costa, Gina L., Lee, Clarence C., Minna, John D., Gazdar, Adi, Birney, Ewan, Rhodes, Michael D., McKernan, Kevin J., Stratton, Michael R., Futreal, Andrew P., and Campbell, Peter J.
Published: 2010
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28. COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer

Author: Forbes, Simon A., Tang, Gurpreet, Bindal, Nidhi, Bamford, Sally, Dawson, Elisabeth, Cole, Charlotte, Kok, Chai Yin, Jia, Mingming, Ewing, Rebecca, Menzies, Andrew, Teague, Jon W., Stratton, Michael R., and Futreal, P. Andrew
Published: 2010
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29. Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis

Author: Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Zooloxía, Xenética e Antropoloxía Física, Petljak, Mia, Alexandrov, Ludmil B., Brammeld, Jonathan S., Price, Stacey, Wedge, David C., Grossmann, Sebastian, Dawson, Kevin J., Ju, Young Seok, Ioro, Francesco, Castro Tubío, José Manuel, Koh, Ching Chiek, Georgakopoulos Soares, Ilias, Rodríguez Martín, Bernardo, Otlu, Burçak, O'Meara, Sarah, Butler, Adam P., Menzies, Andrew, Bhosle, Shriram G., Raine, Keiran, Jones, David R., Teague, Jon W., Beal, Kathryn, Latimer, Calli, O'Neill, Laura, Zamora Berna, Jorge Aurelio, Anderson, Elizabeth, Patel, Nikita, Maddison, Mark, Ng, Bee Ling, Graham, Jennifer, Garnett, Mathew J., McDermott, Ultan, Nik Zainal, Serena, Campbell, Peter J., Stratton, Michael R., Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Zooloxía, Xenética e Antropoloxía Física, Petljak, Mia, Alexandrov, Ludmil B., Brammeld, Jonathan S., Price, Stacey, Wedge, David C., Grossmann, Sebastian, Dawson, Kevin J., Ju, Young Seok, Ioro, Francesco, Castro Tubío, José Manuel, Koh, Ching Chiek, Georgakopoulos Soares, Ilias, Rodríguez Martín, Bernardo, Otlu, Burçak, O'Meara, Sarah, Butler, Adam P., Menzies, Andrew, Bhosle, Shriram G., Raine, Keiran, Jones, David R., Teague, Jon W., Beal, Kathryn, Latimer, Calli, O'Neill, Laura, Zamora Berna, Jorge Aurelio, Anderson, Elizabeth, Patel, Nikita, Maddison, Mark, Ng, Bee Ling, Graham, Jennifer, Garnett, Mathew J., McDermott, Ultan, Nik Zainal, Serena, Campbell, Peter J., and Stratton, Michael R.
Abstract: Multiple signatures of somatic mutations have beenidentified in cancer genomes. Exome sequences of1,001 human cancer cell lines and 577 xenograftsrevealed most common mutational signatures,indicating past activity of the underlying processes,usually in appropriate cancer types. To investigateongoing patterns of mutational-signature genera-tion, cell lines were cultured for extended periodsand subsequently DNA sequenced. Signatures ofdiscontinued exposures, including tobacco smokeand ultraviolet light, were not generatedin vitro. Sig-natures of normal and defective DNA repair and repli-cation continued to be generated at roughly stablemutation rates. Signatures of APOBEC cytidinedeaminase DNA-editing exhibited substantial fluctu-ations in mutation rate over time with episodic burstsof mutations. The initiating factors for the burstsare unclear, although retrotransposon mobilizationmay contribute. The examined cell lines constitutea resource of live experimental models of mutationalprocesses, which potentially retain patterns ofactivity and regulation operative in primary humancancers
Published: 2019

30. Author Correction: Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

Author: Nik-Zainal, Serena, Davies, Helen, Staaf, Johan, Ramakrishna, Manasa, Glodzik, Dominik, Zou, Xueqing, Martincorena, Inigo, Alexandrov, Ludmil B, Martin, Sancha, Wedge, David C, Van Loo, Peter, Ju, Young Seok, Smid, Marcel, Brinkman, Arie B, Morganella, Sandro, Aure, Miriam R, Lingjærde, Ole Christian, Langerød, Anita, Ringnér, Markus, Ahn, Sung-Min, Boyault, Sandrine, Brock, Jane E, Broeks, Annegien, Butler, Adam, Desmedt, Christine, Dirix, Luc Y, Dronov, Serge, Fatima, Aquila, Foekens, John A, Gerstung, Moritz, Hooijer, Gerrit K J, Jang, Se Jin, Jones, David R, Kim, Hyung Yong, King, Tari A, Krishnamurthy, Savitri, Lee, Hee Jin, Lee, Jeong-Yeon, Li, Yilong, McLaren, Stuart, Menzies, Andrew, Mustonen, Ville, O'Meara, Sarah, Pauporté, Iris, Pivot, Xavier, Purdie, Colin A, Raine, Keiran, Ramakrishnan, Kamna, Rodríguez-González, Germán FG, Romieu, Gilles, Sieuwerts, Anieta M, Simpson, Peter T, Shepherd, Rebecca, Stebbings, Lucy A, Stefansson, Olafur A, Teague, Jon W, Tommasi, Stefania, Treilleux, Isabelle, Van den Eynden, Gert, Vermeulen, Peter B., Vincent-Salomon, Anne, Yates, Lucy R., Caldas, Carlos, Van't Veer, Laura, Tutt, Andrew M, Knappskog, Stian, Tan, Benita Kiat Tee BK, Jonkers, Jos, Borg, Åke A., Ueno, Naoto T, Sotiriou, Christos, Viari, Alain, Futreal, P Andrew, Campbell, Peter J, Span, Paul N, Van Laere, Steven, Lakhani, Sunil R, Eyfjord, Jorunn E, Thompson, Alastair M, Birney, Ewan, Stunnenberg, Hendrik G, van de Vijver, Marc J, Martens, John W M, Børresen-Dale, Anne Lise, Richardson, Andrea L, Kong, Gu, Thomas, Gilles, Stratton, Michael R, Nik-Zainal, Serena, Davies, Helen, Staaf, Johan, Ramakrishna, Manasa, Glodzik, Dominik, Zou, Xueqing, Martincorena, Inigo, Alexandrov, Ludmil B, Martin, Sancha, Wedge, David C, Van Loo, Peter, Ju, Young Seok, Smid, Marcel, Brinkman, Arie B, Morganella, Sandro, Aure, Miriam R, Lingjærde, Ole Christian, Langerød, Anita, Ringnér, Markus, Ahn, Sung-Min, Boyault, Sandrine, Brock, Jane E, Broeks, Annegien, Butler, Adam, Desmedt, Christine, Dirix, Luc Y, Dronov, Serge, Fatima, Aquila, Foekens, John A, Gerstung, Moritz, Hooijer, Gerrit K J, Jang, Se Jin, Jones, David R, Kim, Hyung Yong, King, Tari A, Krishnamurthy, Savitri, Lee, Hee Jin, Lee, Jeong-Yeon, Li, Yilong, McLaren, Stuart, Menzies, Andrew, Mustonen, Ville, O'Meara, Sarah, Pauporté, Iris, Pivot, Xavier, Purdie, Colin A, Raine, Keiran, Ramakrishnan, Kamna, Rodríguez-González, Germán FG, Romieu, Gilles, Sieuwerts, Anieta M, Simpson, Peter T, Shepherd, Rebecca, Stebbings, Lucy A, Stefansson, Olafur A, Teague, Jon W, Tommasi, Stefania, Treilleux, Isabelle, Van den Eynden, Gert, Vermeulen, Peter B., Vincent-Salomon, Anne, Yates, Lucy R., Caldas, Carlos, Van't Veer, Laura, Tutt, Andrew M, Knappskog, Stian, Tan, Benita Kiat Tee BK, Jonkers, Jos, Borg, Åke A., Ueno, Naoto T, Sotiriou, Christos, Viari, Alain, Futreal, P Andrew, Campbell, Peter J, Span, Paul N, Van Laere, Steven, Lakhani, Sunil R, Eyfjord, Jorunn E, Thompson, Alastair M, Birney, Ewan, Stunnenberg, Hendrik G, van de Vijver, Marc J, Martens, John W M, Børresen-Dale, Anne Lise, Richardson, Andrea L, Kong, Gu, Thomas, Gilles, and Stratton, Michael R
Abstract: In the Methods section of this Article, 'greater than' should have been 'less than' in the sentence 'Putative regions of clustered rearrangements were identified as having an average inter-rearrangement distance that was at least 10 times greater than the whole-genome average for the individual sample. '. The Article has not been corrected., SCOPUS: er.j, info:eu-repo/semantics/published
Published: 2019

31. Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis

Author: Petljak, Mia, primary, Alexandrov, Ludmil B., additional, Brammeld, Jonathan S., additional, Price, Stacey, additional, Wedge, David C., additional, Grossmann, Sebastian, additional, Dawson, Kevin J., additional, Ju, Young Seok, additional, Iorio, Francesco, additional, Tubio, Jose M.C., additional, Koh, Ching Chiek, additional, Georgakopoulos-Soares, Ilias, additional, Rodríguez–Martín, Bernardo, additional, Otlu, Burçak, additional, O’Meara, Sarah, additional, Butler, Adam P., additional, Menzies, Andrew, additional, Bhosle, Shriram G., additional, Raine, Keiran, additional, Jones, David R., additional, Teague, Jon W., additional, Beal, Kathryn, additional, Latimer, Calli, additional, O’Neill, Laura, additional, Zamora, Jorge, additional, Anderson, Elizabeth, additional, Patel, Nikita, additional, Maddison, Mark, additional, Ng, Bee Ling, additional, Graham, Jennifer, additional, Garnett, Mathew J., additional, McDermott, Ultan, additional, Nik-Zainal, Serena, additional, Campbell, Peter J., additional, and Stratton, Michael R., additional
Published: 2019
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32. Classification and Personalized Prognosis in Myeloproliferative Neoplasms

Author: Grinfeld, Jacob, Nangalia, Jyoti, Baxter, E Joanna, Wedge, David C, Angelopoulos, Nicos, Cantrill, Robert, Godfrey, Anna L, Papaemmanuil, Elli, Gundem, Gunes, MacLean, Cathy, Cook, Julia, O'Neil, Laura, O'Meara, Sarah, Teague, Jon W, Butler, Adam P, Massie, Charlie E, Williams, Nicholas, Nice, Francesca L, Andersen, Christen L, Hasselbalch, Hans C, Guglielmelli, Paola, McMullin, Mary F, Vannucchi, Alessandro M, Harrison, Claire N, Gerstung, Moritz, Green, Anthony R, Campbell, Peter J, Grinfeld, Jacob, Nangalia, Jyoti, Baxter, E Joanna, Wedge, David C, Angelopoulos, Nicos, Cantrill, Robert, Godfrey, Anna L, Papaemmanuil, Elli, Gundem, Gunes, MacLean, Cathy, Cook, Julia, O'Neil, Laura, O'Meara, Sarah, Teague, Jon W, Butler, Adam P, Massie, Charlie E, Williams, Nicholas, Nice, Francesca L, Andersen, Christen L, Hasselbalch, Hans C, Guglielmelli, Paola, McMullin, Mary F, Vannucchi, Alessandro M, Harrison, Claire N, Gerstung, Moritz, Green, Anthony R, and Campbell, Peter J
Abstract: BACKGROUND: Myeloproliferative neoplasms, such as polycythemia vera, essential thrombocythemia, and myelofibrosis, are chronic hematologic cancers with varied progression rates. The genomic characterization of patients with myeloproliferative neoplasms offers the potential for personalized diagnosis, risk stratification, and treatment.METHODS: We sequenced coding exons from 69 myeloid cancer genes in patients with myeloproliferative neoplasms, comprehensively annotating driver mutations and copy-number changes. We developed a genomic classification for myeloproliferative neoplasms and multistage prognostic models for predicting outcomes in individual patients. Classification and prognostic models were validated in an external cohort.RESULTS: A total of 2035 patients were included in the analysis. A total of 33 genes had driver mutations in at least 5 patients, with mutations in JAK2, CALR, or MPL being the sole abnormality in 45% of the patients. The numbers of driver mutations increased with age and advanced disease. Driver mutations, germline polymorphisms, and demographic variables independently predicted whether patients received a diagnosis of essential thrombocythemia as compared with polycythemia vera or a diagnosis of chronic-phase disease as compared with myelofibrosis. We defined eight genomic subgroups that showed distinct clinical phenotypes, including blood counts, risk of leukemic transformation, and event-free survival. Integrating 63 clinical and genomic variables, we created prognostic models capable of generating personally tailored predictions of clinical outcomes in patients with chronic-phase myeloproliferative neoplasms and myelofibrosis. The predicted and observed outcomes correlated well in internal cross-validation of a training cohort and in an independent external cohort. Even within individual categories of existing prognostic schemas, our models substantially improved predictive accuracy.CONCLUSIONS: Comprehensive
Published: 2018

33. Classification and Personalized Prognosis in Myeloproliferative Neoplasms

Author: Grinfeld, Jacob, primary, Nangalia, Jyoti, additional, Baxter, E. Joanna, additional, Wedge, David C., additional, Angelopoulos, Nicos, additional, Cantrill, Robert, additional, Godfrey, Anna L., additional, Papaemmanuil, Elli, additional, Gundem, Gunes, additional, MacLean, Cathy, additional, Cook, Julia, additional, O’Neil, Laura, additional, O’Meara, Sarah, additional, Teague, Jon W., additional, Butler, Adam P., additional, Massie, Charlie E., additional, Williams, Nicholas, additional, Nice, Francesca L., additional, Andersen, Christen L., additional, Hasselbalch, Hans C., additional, Guglielmelli, Paola, additional, McMullin, Mary F., additional, Vannucchi, Alessandro M., additional, Harrison, Claire N., additional, Gerstung, Moritz, additional, Green, Anthony R., additional, and Campbell, Peter J., additional
Published: 2018
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34. A small cell lung cancer genome reports complex tobacco exposure signatures

Author: Pleasance, Erin D, Stephens, Philip J, O'Meara, Sarah, McBride, David J, Meynert, Alison, Jones, David, Lin, Meng-Lay, Beare, David, Lau, King Wai, Greenman, Chris, Varela, Ignacio, Nik-Zainal, Serena, Davies, Helen R, Ordoñez, Gonzalo R, Mudie, Laura J, Latimer, Calli, Edkins, Sarah, Stebbings, Lucy, Chen, Lina, Jia, Mingming, Leroy, Catherine, Marshall, John, Menzies, Andrew, Butler, Adam, Teague, Jon W, Mangion, Jonathon, Sun, Yongming A, McLaughlin, Stephen F, Peckham, Heather E, Tsung, Eric F, Costa, Gina L, Lee, Clarence C, Minna, John D, Gazdar, Adi, Birney, Ewan, Rhodes, Michael D, McKernan, Kevin J, Stratton, Michael R, Futreal, P Andrew, and Campbell, Peter J
Subjects: Lung Neoplasms, DNA Copy Number Variations, DNA Repair, Genome, Human, DNA Mutational Analysis, Smoking, DNA Helicases, Exons, Small Cell Lung Carcinoma, Article, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Mutagenesis, Insertional, Cell Line, Tumor, Mutation, Tobacco, Carcinogens, Humans, Promoter Regions, Genetic, DNA Damage, Sequence Deletion
Abstract: Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in frame, and another two lines carrying PVT1-CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.
Published: 2009

35. Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Author: Behjati, Sam, primary, Tarpey, Patrick S., additional, Haase, Kerstin, additional, Ye, Hongtao, additional, Young, Matthew D., additional, Alexandrov, Ludmil B., additional, Farndon, Sarah J., additional, Collord, Grace, additional, Wedge, David C., additional, Martincorena, Inigo, additional, Cooke, Susanna L., additional, Davies, Helen, additional, Mifsud, William, additional, Lidgren, Mathias, additional, Martin, Sancha, additional, Latimer, Calli, additional, Maddison, Mark, additional, Butler, Adam P., additional, Teague, Jon W., additional, Pillay, Nischalan, additional, Shlien, Adam, additional, McDermott, Ultan, additional, Futreal, P. Andrew, additional, Baumhoer, Daniel, additional, Zaikova, Olga, additional, Bjerkehagen, Bodil, additional, Myklebost, Ola, additional, Amary, M. Fernanda, additional, Tirabosco, Roberto, additional, Van Loo, Peter, additional, Stratton, Michael R., additional, Flanagan, Adrienne M., additional, and Campbell, Peter J., additional
Published: 2017
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36. ascatNgs: Identifying Somatically Acquired Copy‐Number Alterations from Whole‐Genome Sequencing Data

Author: Raine, Keiran M., primary, Van Loo, Peter, additional, Wedge, David C., additional, Jones, David, additional, Menzies, Andrew, additional, Butler, Adam P., additional, Teague, Jon W., additional, Tarpey, Patrick, additional, Nik‐Zainal, Serena, additional, and Campbell, Peter J., additional
Published: 2016
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37. cgpCaVEManWrapper: Simple Execution of CaVEMan in Order to Detect Somatic Single Nucleotide Variants in NGS Data

Author: Jones, David, primary, Raine, Keiran M., additional, Davies, Helen, additional, Tarpey, Patrick S., additional, Butler, Adam P., additional, Teague, Jon W., additional, Nik‐Zainal, Serena, additional, and Campbell, Peter J., additional
Published: 2016
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38. Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

Author: Nik-Zainal, Serena, Davies, Helen, Staaf, Johan, Ramakrishna, Manasa, Glodzik, Dominik, Zou, Xueqing, Martincorena, Inigo, Alexandrov, Ludmil B, Martin, Sancha, Wedge, David C, Van Loo, Peter, Ju, Young Seok, Smid, Michiel M., Brinkman, Arie B, Morganella, Sandro, Aure, Miriam R, Lingjærde, Ole Christian, Langerød, Anita, Ringnér, Markus, Ahn, Sung-Min, Boyault, Sandrine, Brock, Jane E, Broeks, Annegien, Butler, Adam, Desmedt, Christine, Dirix, Luc Y, Dronov, Serge, Fatima, Aquila, Foekens, John A, Gerstung, Moritz, Hooijer, Gerrit GK, Jang, Se Jin, Jones, David R, Kim, Hyung Yong, King, Tari TA, Krishnamurthy, Savitri, Lee, Hee Jin, Lee, Jeong-Yeon, Li, Yilong, McLaren, Stuart, Menzies, Andrew, Mustonen, Ville, O'Meara, Sarah, Pauporté, Iris, Pivot, Xavier, Purdie, Colin CA, Raine, Keiran, Ramakrishnan, Kamna, Rodríguez-González, Germán FG, Romieu, Gilles, Sieuwerts, Anieta M, Simpson, Peter PT, Shepherd, Rebecca, Stebbings, Lucy A, Stefansson, Olafur OA, Teague, Jon W, Tommasi, Stefania, Treilleux, Isabelle, Van den Eynden, Gert, Vermeulen, Peter B., Vincent-Salomon, Anne, Yates, Lucy R., Caldas, Carlos, Van't Veer, Laura, Tutt, Andrew M, Knappskog, Stian, Tan, Benita Kiat Tee BK, Jonkers, Jos, Borg, Åke A., Ueno, Naoto T, Sotiriou, Christos, Viari, Alain, Futreal, P Andrew, Campbell, Peter J, Span, Paul N, Van Laere, Steven, Lakhani, Sunil R, Eyfjörd, Jórunn Erla, Thompson, Alastair M, Birney, Ewan, Stunnenberg, Hendrik G, Van de Vijver, Marc J, Martens, John W M, Børresen-Dale, Anne Lise, Richardson, Andrea L, Kong, Gu, Thomas, Gilles, Stratton, Michael R, Nik-Zainal, Serena, Davies, Helen, Staaf, Johan, Ramakrishna, Manasa, Glodzik, Dominik, Zou, Xueqing, Martincorena, Inigo, Alexandrov, Ludmil B, Martin, Sancha, Wedge, David C, Van Loo, Peter, Ju, Young Seok, Smid, Michiel M., Brinkman, Arie B, Morganella, Sandro, Aure, Miriam R, Lingjærde, Ole Christian, Langerød, Anita, Ringnér, Markus, Ahn, Sung-Min, Boyault, Sandrine, Brock, Jane E, Broeks, Annegien, Butler, Adam, Desmedt, Christine, Dirix, Luc Y, Dronov, Serge, Fatima, Aquila, Foekens, John A, Gerstung, Moritz, Hooijer, Gerrit GK, Jang, Se Jin, Jones, David R, Kim, Hyung Yong, King, Tari TA, Krishnamurthy, Savitri, Lee, Hee Jin, Lee, Jeong-Yeon, Li, Yilong, McLaren, Stuart, Menzies, Andrew, Mustonen, Ville, O'Meara, Sarah, Pauporté, Iris, Pivot, Xavier, Purdie, Colin CA, Raine, Keiran, Ramakrishnan, Kamna, Rodríguez-González, Germán FG, Romieu, Gilles, Sieuwerts, Anieta M, Simpson, Peter PT, Shepherd, Rebecca, Stebbings, Lucy A, Stefansson, Olafur OA, Teague, Jon W, Tommasi, Stefania, Treilleux, Isabelle, Van den Eynden, Gert, Vermeulen, Peter B., Vincent-Salomon, Anne, Yates, Lucy R., Caldas, Carlos, Van't Veer, Laura, Tutt, Andrew M, Knappskog, Stian, Tan, Benita Kiat Tee BK, Jonkers, Jos, Borg, Åke A., Ueno, Naoto T, Sotiriou, Christos, Viari, Alain, Futreal, P Andrew, Campbell, Peter J, Span, Paul N, Van Laere, Steven, Lakhani, Sunil R, Eyfjörd, Jórunn Erla, Thompson, Alastair M, Birney, Ewan, Stunnenberg, Hendrik G, Van de Vijver, Marc J, Martens, John W M, Børresen-Dale, Anne Lise, Richardson, Andrea L, Kong, Gu, Thomas, Gilles, and Stratton, Michael R
Abstract: We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2016

39. Processed pseudogenes acquired somatically during cancer development

Author: Cooke, Susanna L., Shlien, Adam, Marshall, John, Pipinikas, Christodoulos P., Martincorena, Inigo, Tubio, Jose M.C., Li, Yilong, Menzies, Andrew, Mudie, Laura, Ramakrishna, Manasa, Yates, Lucy, Davies, Helen, Bolli, Niccolo, Bignell, Graham R., Tarpey, Patrick S., Behjati, Sam, Nik-Zainal, Serena, Papaemmanuil, Elli, Teixeira, Vitor H., Raine, Keiran, O’Meara, Sarah, Dodoran, Maryam S., Teague, Jon W., Butler, Adam P., Iacobuzio-Donahue, Christine, Santarius, Thomas, Grundy, Richard G., Malkin, David, Greaves, Mel, Munshi, Nikhil, Flanagan, Adrienne M., Bowtell, David, Martin, Sancha, Larsimont, Denis, Reis-Filho, Jorge S., Boussioutas, Alex, Taylor, Jack, Hayes, Neil D., Janes, Sam M., Futreal, P. Andrew, Stratton, Michael R., McDermott, Ultan, Campbell, Peter J., Provenzano, Elena, van de Vijver, Marc, Richardson, Andrea L., Purdie, Colin, Pinder, Sarah, Mac Grogan, Gaetan, Vincent-Salomon, Anne, Grabau, Dorthe, Sauer, Torill, Garred, Øystein, Ehinger, Anna, Van den Eynden, Gert G., van Deurzen, C.H.M, Salgado, Roberto, Brock, Jane E., Lakhani, Sunil R., Giri, Dilip D., Arnould, Laurent, Jacquemier, Jocelyne, Treilleux, Isabelle, Caldas, Carlos, Chin, Suet-Feung, Fatima, Aquila, Thompson, Alastair M., Stenhouse, Alasdair, Foekens, John, Martens, John, Sieuwerts, Anieta, Brinkman, Arjen, Stunnenberg, Henk, Span, Paul N., Sweep, Fred, Desmedt, Christine, Sotiriou, Christos, Thomas, Gilles, Broeks, Annegein, Langerod, Anita, Aparicio, Samuel, Simpson, Peter T., van ’t Veer, Laura, Erla Eyfjörd, Jórunn, Hilmarsdottir, Holmfridur, Jonasson, Jon G., Børresen-Dale, Anne-Lise, Lee, Ming Ta Michael, Wong, Bernice Huimin, Tan, Benita Kiat Tee, Hooijer, Gerrit K.J., Pathology, Cancer Center Amsterdam, Nik-Zainal, Serena [0000-0001-5054-1727], Apollo - University of Cambridge Repository, and 1Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. 2Lungs for Living Research Centre, Rayne Institute, University College London, London WC1E 6JF, UK. 31] Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK [2] University of Cambridge, Cambridge CB2 0XY, UK. 4Departments of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA. 5Addenbrooke's NHS Foundation Trust, Cambridge CB2 0QQ, UK. 6Children's Brain Tumour Research Centre, University of Nottingham, Nottingham NG7 2UH, UK. 7Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8. 8Institute for Cancer Research, Sutton, London SM2 5NG, UK. 9Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 101] Lungs for Living Research Centre, Rayne Institute, University College London, London WC1E 6JF, UK [2] Royal National Orthopaedic Hospital, Middlesex HA7 4LP, UK. 11Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia. 12Department of Pathology, Memorial-Sloan-Kettering Cancer Center, New York, New York 10065, USA. 131] Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia [2] Department of Gastroenterology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria 3050, Australia. 14National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27713, USA. 15UNC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA. 161] Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK [2] Addenbrooke's NHS Foundation Trust, Cambridge CB2 0QQ, UK. 171] Cancer Genome Project, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK [2] University of Cambridge, Cambridge CB2 0XY, UK [3] Addenbrooke's NHS Foundation Trust, Cambridge CB2 0QQ, UK.
Subjects: Gene Expression Regulation, Neoplastic -- genetics -- physiology, Lung Neoplasms, Pseudogene, General Physics and Astronomy, Gene Expression, Retrotransposon, Context (language use), Breast Neoplasms, Biology, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, Germline, Exon, Neoplasms, medicine, Humans, Hvítblæði, Gene, Krabbamein, Genetics, Mutation, Multidisciplinary, Neoplasms -- genetics, Cancer, Médecine pathologie humaine, Brain, General Chemistry, medicine.disease, 3. Good health, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Cancérologie, Gene Expression Regulation, Neoplastic, Pseudogenes -- genetics -- physiology, Pseudogenes
Abstract: Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5' truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2014

40. Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer

Author: Nangalia, Jyoti, Gerstung, Moritz, Alexandrov, Ludmil B, Davies, Helen R, Teague, Jon W, Grundy, Richard, Shlien, Adam, Bolli, Niccolo, Unnikrishnan, Ashwin, Vassiliou, George S, Ju, Young Seok, Greaves, Mel, Green, Anthony R, Collins, V Peter, Gundem, Gunes, Behjati, Sam, Massie, Charles E, Santarius, Tom, Du, Ming-Qing, Pimanda, John E, Papaemmanuil, Elli, Munshi, Nikhil, Martincorena, Inigo, Teh, Bin Tean, Vyas, Paresh, Nik-Zainal, Serena, El-Naggar, Adel K, Hayes, D Neil, Taylor, Jack A, Ramakrishna, Manasa, Butler, Adam P, and Tarpey, Patrick S
Abstract: Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria and is fundamentally linked to mtDNA replication.
Published: 2014
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41. Genomic Classification and Prognosis in Acute Myeloid Leukemia

Author: Papaemmanuil, Elli, primary, Gerstung, Moritz, additional, Bullinger, Lars, additional, Gaidzik, Verena I., additional, Paschka, Peter, additional, Roberts, Nicola D., additional, Potter, Nicola E., additional, Heuser, Michael, additional, Thol, Felicitas, additional, Bolli, Niccolo, additional, Gundem, Gunes, additional, Van Loo, Peter, additional, Martincorena, Inigo, additional, Ganly, Peter, additional, Mudie, Laura, additional, McLaren, Stuart, additional, O’Meara, Sarah, additional, Raine, Keiran, additional, Jones, David R., additional, Teague, Jon W., additional, Butler, Adam P., additional, Greaves, Mel F., additional, Ganser, Arnold, additional, Döhner, Konstanze, additional, Schlenk, Richard F., additional, Döhner, Hartmut, additional, and Campbell, Peter J., additional
Published: 2016
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42. VAGrENT: Variation Annotation Generator

Author: Menzies, Andy, primary, Teague, Jon W., additional, Butler, Adam P., additional, Davies, Helen, additional, Tarpey, Patrick, additional, Nik‐Zainal, Serena, additional, and Campbell, Peter J., additional
Published: 2015
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43. cgpPindel: Identifying Somatically Acquired Insertion and Deletion Events from Paired End Sequencing

Author: Raine, Keiran M., primary, Hinton, Jonathan, additional, Butler, Adam P., additional, Teague, Jon W., additional, Davies, Helen, additional, Tarpey, Patrick, additional, Nik‐Zainal, Serena, additional, and Campbell, Peter J., additional
Published: 2015
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44. Signatures of mutational processes in human cancer

Author: Alexandrov, Ludmil B, Nik-Zainal, Serena, Wedge, David C, Aparicio, Samuel AJR, Behjati, Sam, Biankin, Andrew V, Bignell, Graham R, Bolli, Niccolò, Borg, Ake, Børresen-Dale, Anne-Lise, Boyault, Sandrine, Burkhardt, Birgit, Butler, Adam P, Caldas, Carlos, Davies, Helen R, Desmedt, Christine, Eils, Roland, Eyfjörd, Jórunn Erla, Foekens, John A, Greaves, Mel, Hosoda, Fumie, Hutter, Barbara, Ilicic, Tomislav, Imbeaud, Sandrine, Imielinski, Marcin, Jäger, Natalie, Jones, David TW, Jones, David, Knappskog, Stian, Kool, Marcel, Lakhani, Sunil R, López-Otín, Carlos, Martin, Sancha, Munshi, Nikhil C, Nakamura, Hiromi, Northcott, Paul A, Pajic, Marina, Papaemmanuil, Elli, Paradiso, Angelo, Pearson, John V, Puente, Xose S, Raine, Keiran, Ramakrishna, Manasa, Richardson, Andrea L, Richter, Julia, Rosenstiel, Philip, Schlesner, Matthias, Schumacher, Ton N, Span, Paul N, Teague, Jon W, Totoki, Yasushi, Tutt, Andrew NJ, Valdés-Mas, Rafael, van Buuren, Marit M, van 't Veer, Laura, Vincent-Salomon, Anne, Waddell, Nicola, Yates, Lucy R, Australian Pancreatic Cancer Genome Initiative, ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, ICGC PedBrain, Zucman-Rossi, Jessica, Futreal, P Andrew, McDermott, Ultan, Lichter, Peter, Meyerson, Matthew, Grimmond, Sean M, Siebert, Reiner, Campo, Elías, Shibata, Tatsuhiro, Pfister, Stefan M, Campbell, Peter J, Stratton, Michael R, Nik-Zainal Abidin, Serena [0000-0001-5054-1727], Caldas, Carlos [0000-0003-3547-1489], and Apollo - University of Cambridge Repository
Subjects: Aging, Models, Genetic, Transcription, Genetic, DNA Mutational Analysis, Reproducibility of Results, DNA, Mutagenesis, Insertional, Cell Transformation, Neoplastic, Mutagenesis, Organ Specificity, Cytidine Deaminase, Neoplasms, Mutation, Humans, Algorithms, Mutagens, Sequence Deletion
Abstract: All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
Published: 2013

45. The Life History of 21 Breast Cancers

Author: Nik-Zainal, Serena, primary, Van Loo, Peter, additional, Wedge, David C., additional, Alexandrov, Ludmil B., additional, Greenman, Christopher D., additional, Lau, King Wai, additional, Raine, Keiran, additional, Jones, David, additional, Marshall, John, additional, Ramakrishna, Manasa, additional, Shlien, Adam, additional, Cooke, Susanna L., additional, Hinton, Jonathan, additional, Menzies, Andrew, additional, Stebbings, Lucy A., additional, Leroy, Catherine, additional, Jia, Mingming, additional, Rance, Richard, additional, Mudie, Laura J., additional, Gamble, Stephen J., additional, Stephens, Philip J., additional, McLaren, Stuart, additional, Tarpey, Patrick S., additional, Papaemmanuil, Elli, additional, Davies, Helen R., additional, Varela, Ignacio, additional, McBride, David J., additional, Bignell, Graham R., additional, Leung, Kenric, additional, Butler, Adam P., additional, Teague, Jon W., additional, Martin, Sancha, additional, Jönsson, Goran, additional, Mariani, Odette, additional, Boyault, Sandrine, additional, Miron, Penelope, additional, Fatima, Aquila, additional, Langerød, Anita, additional, Aparicio, Samuel A.J.R., additional, Tutt, Andrew, additional, Sieuwerts, Anieta M., additional, Borg, Åke, additional, Thomas, Gilles, additional, Salomon, Anne Vincent, additional, Richardson, Andrea L., additional, Børresen-Dale, Anne-Lise, additional, Futreal, P. Andrew, additional, Stratton, Michael R., additional, and Campbell, Peter J., additional
Published: 2015
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46. A small-cell lung cancer genome with complex signatures of tobacco exposure

Author: Pleasance, Erin D, Stephens, Philip J, O'Meara, Sarah, McBride, David J, Meynert, Alison, Jones, David, Lin, Meng-Lay, Beare, David, Lau, King Wai, Greenman, Chris, Varela, Ignacio, Nik-Zainal, Serena, Davies, Helen R, Ordoñez, Gonzalo R, Mudie, Laura J, Latimer, Calli, Edkins, Sarah, Stebbings, Lucy, Chen, Lina, Jia, Mingming, Leroy, Catherine, Marshall, John, Menzies, Andrew, Butler, Adam, Teague, Jon W, Mangion, Jonathon, Sun, Yongming A, McLaughlin, Stephen F, Peckham, Heather E, Tsung, Eric F, Costa, Gina L, Lee, Clarence C, Minna, John D, Gazdar, Adi, Birney, Ewan, Rhodes, Michael D, McKernan, Kevin J, Stratton, Michael R, Futreal, P Andrew, Campbell, Peter J, Nik-Zainal, Serena [0000-0001-5054-1727], and Apollo - University of Cambridge Repository
Subjects: Lung Neoplasms, DNA Copy Number Variations, DNA Repair, Genome, Human, DNA Mutational Analysis, Smoking, DNA Helicases, Exons, Small Cell Lung Carcinoma, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Mutagenesis, Insertional, Cell Line, Tumor, Mutation, Tobacco, Carcinogens, Humans, Promoter Regions, Genetic, DNA Damage, Sequence Deletion
Abstract: Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in frame, and another two lines carrying PVT1-CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.
Published: 2010

47. Processed pseudogenes acquired somatically during cancer development.

Author: Cooke, Susanna S.L., Shlien, Adam, Marshall, John, Pipinikas, Christodoulos P, Martincorena, Inigo, Tubio, Jose M C, Li, Yilong, Menzies, Andrew, Mudie, Laura, Ramakrishna, Manasa, Yates, Lucy R., Davies, Helen, Bolli, Niccolo, Bignell, Graham R, Tarpey, Patrick S, Behjati, Sam, Nik-Zainal, Serena, Papaemmanuil, Elli, Teixeira, Vitor H, Raine, Keiran, O'Meara, Sarah, Dodoran, Maryam S, Teague, Jon W, Butler, Adam P, Iacobuzio-Donahue, Christine, Santarius, Thomas, Grundy, Richard G, Malkin, David, Greaves, Mel, Munshi, Nikhil, Flanagan, Adrienne M, Bowtell, David, Martin, Sancha, Larsimont, Denis, Reis-Filho, Jorge Sergio, Boussioutas, Alex, Taylor, Jack A, Hayes, Neil D, Janes, Sam M, Futreal, P Andrew, Stratton, Michael R, McDermott, Ultan, Campbell, Peter J, ICGC Breast Cancer Group, Cooke, Susanna S.L., Shlien, Adam, Marshall, John, Pipinikas, Christodoulos P, Martincorena, Inigo, Tubio, Jose M C, Li, Yilong, Menzies, Andrew, Mudie, Laura, Ramakrishna, Manasa, Yates, Lucy R., Davies, Helen, Bolli, Niccolo, Bignell, Graham R, Tarpey, Patrick S, Behjati, Sam, Nik-Zainal, Serena, Papaemmanuil, Elli, Teixeira, Vitor H, Raine, Keiran, O'Meara, Sarah, Dodoran, Maryam S, Teague, Jon W, Butler, Adam P, Iacobuzio-Donahue, Christine, Santarius, Thomas, Grundy, Richard G, Malkin, David, Greaves, Mel, Munshi, Nikhil, Flanagan, Adrienne M, Bowtell, David, Martin, Sancha, Larsimont, Denis, Reis-Filho, Jorge Sergio, Boussioutas, Alex, Taylor, Jack A, Hayes, Neil D, Janes, Sam M, Futreal, P Andrew, Stratton, Michael R, McDermott, Ultan, Campbell, Peter J, and ICGC Breast Cancer Group
Abstract: Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5' truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2014

48. Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes.

Author: Tubio, Jose M C, Li, Yilong, Ju, Young Seok, Martincorena, Inigo, Cooke, Susanna S.L., Tojo, Marta, Gundem, Gunes, Pipinikas, Christodoulos P, Zamora, Jorge, Raine, Keiran, Menzies, Andrew, Roman-Garcia, Pablo, Fullam, Anthony, Gerstung, Moritz, Shlien, Adam, Tarpey, Patrick S, Papaemmanuil, Elli, Knappskog, Stian, Van Loo, Peter, Ramakrishna, Manasa, Davies, Helen, Marshall, John, Wedge, David C., Teague, Jon W, Butler, Adam P, Nik-Zainal, Serena, Alexandrov, Ludmil, Behjati, Sam, Yates, Lucy R., Bolli, Niccolo, Mudie, Laura, Hardy, Claire, Martin, Sancha, McLaren, Stuart, O'Meara, Sarah, Anderson, Elizabeth, Maddison, Mark, Gamble, Stephen, ICGC Breast Cancer Group, ICGC Bone Cancer Group, ICGC Prostate Cancer Group, Foster, Christopher, Warren, Anne Y, Whitaker, Hayley, Brewer, Daniel, Eeles, Rosalind, Cooper, Colin, Neal, David, Lynch, Andy G, Visakorpi, Tapio, Isaacs, William WB, Van't Veer, Laura, Caldas, Carlos, Desmedt, Christine, Sotiriou, Christos, Aparicio, Samuel, Foekens, John A, Eyfjörd, Jórunn Erla, Lakhani, Sunil R, Thomas, Gilles, Myklebost, Ola, Span, Paul, Børresen-Dale, A L, Richardson, Andrea L, Van de Vijver, Marc J, Vincent-Salomon, Anne, Van den Eynden, Gert, Flanagan, Adrienne M, Futreal, P Andrew, Janes, Sam M, Bova, Steven GS, Stratton, Michael R, McDermott, Ultan, Campbell, Peter J, Tubio, Jose M C, Li, Yilong, Ju, Young Seok, Martincorena, Inigo, Cooke, Susanna S.L., Tojo, Marta, Gundem, Gunes, Pipinikas, Christodoulos P, Zamora, Jorge, Raine, Keiran, Menzies, Andrew, Roman-Garcia, Pablo, Fullam, Anthony, Gerstung, Moritz, Shlien, Adam, Tarpey, Patrick S, Papaemmanuil, Elli, Knappskog, Stian, Van Loo, Peter, Ramakrishna, Manasa, Davies, Helen, Marshall, John, Wedge, David C., Teague, Jon W, Butler, Adam P, Nik-Zainal, Serena, Alexandrov, Ludmil, Behjati, Sam, Yates, Lucy R., Bolli, Niccolo, Mudie, Laura, Hardy, Claire, Martin, Sancha, McLaren, Stuart, O'Meara, Sarah, Anderson, Elizabeth, Maddison, Mark, Gamble, Stephen, ICGC Breast Cancer Group, ICGC Bone Cancer Group, ICGC Prostate Cancer Group, Foster, Christopher, Warren, Anne Y, Whitaker, Hayley, Brewer, Daniel, Eeles, Rosalind, Cooper, Colin, Neal, David, Lynch, Andy G, Visakorpi, Tapio, Isaacs, William WB, Van't Veer, Laura, Caldas, Carlos, Desmedt, Christine, Sotiriou, Christos, Aparicio, Samuel, Foekens, John A, Eyfjörd, Jórunn Erla, Lakhani, Sunil R, Thomas, Gilles, Myklebost, Ola, Span, Paul, Børresen-Dale, A L, Richardson, Andrea L, Van de Vijver, Marc J, Vincent-Salomon, Anne, Van den Eynden, Gert, Flanagan, Adrienne M, Futreal, P Andrew, Janes, Sam M, Bova, Steven GS, Stratton, Michael R, McDermott, Ultan, and Campbell, Peter J
Abstract: Long interspersed nuclear element-1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3' transduction. Because 3' transductions are potentially mutagenic, we explored the extent to which they occur somatically during tumorigenesis. Studying cancer genomes from 244 patients, we found that tumors from 53% of the patients had somatic retrotranspositions, of which 24% were 3' transductions. Fingerprinting of donor L1s revealed that a handful of source L1 elements in a tumor can spawn from tens to hundreds of 3' transductions, which can themselves seed further retrotranspositions. The activity of individual L1 elements fluctuated during tumor evolution and correlated with L1 promoter hypomethylation. The 3' transductions disseminated genes, exons, and regulatory elements to new locations, most often to heterochromatic regions of the genome., SCOPUS: re.j, info:eu-repo/semantics/published
Published: 2014

49. A comprehensive multicenter comparison of whole genome sequencing pipelines using a uniform tumor-normal sample pair

Author: Buchhalter, Ivo, primary, Hutter, Barbara, additional, Alioto, Tyler S, additional, Beck, Timothy A, additional, Boutros, Paul C, additional, Brors, Benedikt, additional, Butler, Adam P, additional, Chotewutmontri, Sasithorn, additional, Denroche, Robert E, additional, Derdak, Sophia, additional, Diessl, Nicolle, additional, Feuerbach, Lars, additional, Fujimoto, Akihiro, additional, Gröbner, Susanne, additional, Gut, Marta, additional, Harding, Nicholas J, additional, Heinold, Michael, additional, Heisler, Lawrence E, additional, Hinton, Jonathan, additional, Jäger, Natalie, additional, Jones, David, additional, Kabbe, Rolf, additional, Korshunov, Andrey, additional, McPherson, John D, additional, Menzies, Andrew, additional, Nakagawa, Hidewaki, additional, Previti, Christopher, additional, Raine, Keiran, additional, Ribeca, Paolo, additional, Schmidt, Sabine, additional, Shepherd, Rebecca, additional, Stebbings, Lucy, additional, Tarpey, Patrick S, additional, Teague, Jon W, additional, Tonon, Laurie, additional, Wheeler, David A, additional, Xi, Liu, additional, Yamaguchi, Takafumi N, additional, Sertier, Anne-Sophie, additional, Pfister, Stefan M, additional, Campbell, Peter J, additional, Schlesner, Matthias, additional, Lichter, Peter, additional, Eils, Roland, additional, Gut, Ivo G, additional, and Jones, David T W, additional
Published: 2014
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50. COSMIC: exploring the world's knowledge of somatic mutations in human cancer

Author: Forbes, Simon A., primary, Beare, David, additional, Gunasekaran, Prasad, additional, Leung, Kenric, additional, Bindal, Nidhi, additional, Boutselakis, Harry, additional, Ding, Minjie, additional, Bamford, Sally, additional, Cole, Charlotte, additional, Ward, Sari, additional, Kok, Chai Yin, additional, Jia, Mingming, additional, De, Tisham, additional, Teague, Jon W., additional, Stratton, Michael R., additional, McDermott, Ultan, additional, and Campbell, Peter J., additional
Published: 2014
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