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112

Cell reports. 2021:34(8).DOI:

Whole-genome characterization of lung adenocarcinomas lacking alterations in the RTK/RAS/RAF pathway (vol 34, 108707-1.e1, 2021) [Correction]

Carrot-Zhang, Jian; Yao, Xiaotong; Devarakonda, Siddhartha; Deshpande, Aditya; Damrauer, Jeffrey S.; Silva, Tiago Chedraoui; Wong, Christopher K.; Choi, Hyo Young; Felau, Ina; Robertson, A. Gordon; Castro, Mauro A. A.; Bao, Lisui; Rheinbay, Esther; Liu, Eric Minwei; Trieu, Tuan; Haan, David; Yau, Christina; Hinoue, Toshinori; Liu, Yuexin; Shapira, Ofer; Kumar, Kiran; Mungall, Karen L.; Zhang, Hailei; Lee, Jake June-Koo; Berger, Ashton; Gao, Galen F.; Zhitomirsky, Binyamin; Liang, Wen-Wei; Zhou, Meng; Moorthi, Sitapriya; Berger, Alice H.; Collisson, Eric A.; Zody, Michael C.; Ding, Li; Cherniack, Andrew D.; Getz, Gad; Elemento, Olivier; Benz, Christopher C.; Stuart, Josh; Zenklusen, J. C.; Beroukhim, Rameen; Chang, Jason C.; Campbell, Joshua D.; Hayes, D. Neil; Yang, Lixing; Laird, Peter W.; Weinstein, John N.; Kwiatkowski, David J.; Tsao, Ming S.; Travis, William D.; Khurana, Ekta; Berman, Benjamin P.; Hoadley, Katherine A.; Robine, Nicolas; Meyerson, Matthew; Govindan, Ramaswamy; Imielinski, Marcin
ISI:000621772300018
ISSN: 2211-1247
CID: 5270752
Molecular cell. 2020:80(4):562-577.DOI: 10.1016/j.molcel.2020.10.033

Impact of Lineage Plasticity to and from a Neuroendocrine Phenotype on Progression and Response in Prostate and Lung Cancers

Rubin, Mark A; Bristow, Robert G; Thienger, Phillip D; Dive, Caroline; Imielinski, Marcin
Intratumoral heterogeneity can occur via phenotype transitions, often after chronic exposure to targeted anticancer agents. This process, termed lineage plasticity, is associated with acquired independence to an initial oncogenic driver, resulting in treatment failure. In non-small cell lung cancer (NSCLC) and prostate cancers, lineage plasticity manifests when the adenocarcinoma phenotype transforms into neuroendocrine (NE) disease. The exact molecular mechanisms involved in this NE transdifferentiation remain elusive. In small cell lung cancer (SCLC), plasticity from NE to nonNE phenotypes is driven by NOTCH signaling. Herein we review current understanding of NE lineage plasticity dynamics, exemplified by prostate cancer, NSCLC, and SCLC.
PMCID:8399907
PMID: 33217316
ISSN: 1097-4164
CID: 5270282
Cell. 2020:183(1):197-210.e32.DOI: 10.1016/j.cell.2020.08.006

Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs

Hadi, Kevin; Yao, Xiaotong; Behr, Julie M; Deshpande, Aditya; Xanthopoulakis, Charalampos; Tian, Huasong; Kudman, Sarah; Rosiene, Joel; Darmofal, Madison; DeRose, Joseph; Mortensen, Rick; Adney, Emily M; Shaiber, Alon; Gajic, Zoran; Sigouros, Michael; Eng, Kenneth; Wala, Jeremiah A; Wrzeszczyński, Kazimierz O; Arora, Kanika; Shah, Minita; Emde, Anne-Katrin; Felice, Vanessa; Frank, Mayu O; Darnell, Robert B; Ghandi, Mahmoud; Huang, Franklin; Dewhurst, Sally; Maciejowski, John; de Lange, Titia; Setton, Jeremy; Riaz, Nadeem; Reis-Filho, Jorge S; Powell, Simon; Knowles, David A; Reznik, Ed; Mishra, Bud; Beroukhim, Rameen; Zody, Michael C; Robine, Nicolas; Oman, Kenji M; Sanchez, Carissa A; Kuhner, Mary K; Smith, Lucian P; Galipeau, Patricia C; Paulson, Thomas G; Reid, Brian J; Li, Xiaohong; Wilkes, David; Sboner, Andrea; Mosquera, Juan Miguel; Elemento, Olivier; Imielinski, Marcin
Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g., deletion) or complex (e.g., chromothripsis) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,778 tumor whole-genome sequences, we uncovered three novel complex rearrangement phenomena: pyrgo, rigma, and tyfonas. Pyrgo are "towers" of low-JCN duplications associated with early-replicating regions, superenhancers, and breast or ovarian cancers. Rigma comprise "chasms" of low-JCN deletions enriched in late-replicating fragile sites and gastrointestinal carcinomas. Tyfonas are "typhoons" of high-JCN junctions and fold-back inversions associated with expressed protein-coding fusions, breakend hypermutation, and acral, but not cutaneous, melanomas. Clustering of tumors according to genome graph-derived features identified subgroups associated with DNA repair defects and poor prognosis.
PMID: 33007263
ISSN: 1097-4172
CID: 4632912
bioRxiv.org : the preprint server for biology. 2020.DOI: 10.1101/2020.04.20.048066

Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions [PrePrint]

Butler, Daniel J; Mozsary, Christopher; Meydan, Cem; Danko, David; Foox, Jonathan; Rosiene, Joel; Shaiber, Alon; Afshinnekoo, Ebrahim; MacKay, Matthew; Sedlazeck, Fritz J; Ivanov, Nikolay A; Sierra, Maria; Pohle, Diana; Zietz, Michael; Gisladottir, Undina; Ramlall, Vijendra; Westover, Craig D; Ryon, Krista; Young, Benjamin; Bhattacharya, Chandrima; Ruggiero, Phyllis; Langhorst, Bradley W; Tanner, Nathan; Gawrys, Justyna; Meleshko, Dmitry; Xu, Dong; Steel, Peter A D; Shemesh, Amos J; Xiang, Jenny; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Schwartz, Robert E; Iftner, Angelika; Bezdan, Daniela; Sipley, John; Cong, Lin; Craney, Arryn; Velu, Priya; Melnick, Ari M; Hajirasouliha, Iman; Horner, Stacy M; Iftner, Thomas; Salvatore, Mirella; Loda, Massimo; Westblade, Lars F; Cushing, Melissa; Levy, Shawn; Wu, Shixiu; Tatonetti, Nicholas; Imielinski, Marcin; Rennert, Hanna; Mason, Christopher E
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets.
PMID: 32511352
ISSN: 2692-8205
CID: 5270272
Nature. 2020:578(7793):102-111.DOI: 10.1038/s41586-020-1965-x

Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

Rheinbay, Esther; Nielsen, Morten Muhlig; Abascal, Federico; Wala, Jeremiah A; Shapira, Ofer; Tiao, Grace; Hornshøj, Henrik; Hess, Julian M; Juul, Randi Istrup; Lin, Ziao; Feuerbach, Lars; Sabarinathan, Radhakrishnan; Madsen, Tobias; Kim, Jaegil; Mularoni, Loris; Shuai, Shimin; Lanzós, Andrés; Herrmann, Carl; Maruvka, Yosef E; Shen, Ciyue; Amin, Samirkumar B; Bandopadhayay, Pratiti; Bertl, Johanna; Boroevich, Keith A; Busanovich, John; Carlevaro-Fita, Joana; Chakravarty, Dimple; Chan, Calvin Wing Yiu; Craft, David; Dhingra, Priyanka; Diamanti, Klev; Fonseca, Nuno A; Gonzalez-Perez, Abel; Guo, Qianyun; Hamilton, Mark P; Haradhvala, Nicholas J; Hong, Chen; Isaev, Keren; Johnson, Todd A; Juul, Malene; Kahles, Andre; Kahraman, Abdullah; Kim, Youngwook; Komorowski, Jan; Kumar, Kiran; Kumar, Sushant; Lee, Donghoon; Lehmann, Kjong-Van; Li, Yilong; Liu, Eric Minwei; Lochovsky, Lucas; Park, Keunchil; Pich, Oriol; Roberts, Nicola D; Saksena, Gordon; Schumacher, Steven E; Sidiropoulos, Nikos; Sieverling, Lina; Sinnott-Armstrong, Nasa; Stewart, Chip; Tamborero, David; Tubio, Jose M C; Umer, Husen M; Uusküla-Reimand, Liis; Wadelius, Claes; Wadi, Lina; Yao, Xiaotong; Zhang, Cheng-Zhong; Zhang, Jing; Haber, James E; Hobolth, Asger; Imielinski, Marcin; Kellis, Manolis; Lawrence, Michael S; von Mering, Christian; Nakagawa, Hidewaki; Raphael, Benjamin J; Rubin, Mark A; Sander, Chris; Stein, Lincoln D; Stuart, Joshua M; Tsunoda, Tatsuhiko; Wheeler, David A; Johnson, Rory; Reimand, Jüri; Gerstein, Mark; Khurana, Ekta; Campbell, Peter J; López-Bigas, Núria; Weischenfeldt, Joachim; Beroukhim, Rameen; Martincorena, Iñigo; Pedersen, Jakob Skou; Getz, Gad
The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
PMID: 32025015
ISSN: 1476-4687
CID: 5270262
Nature. 2020:578(7793):112-121.DOI: 10.1038/s41586-019-1913-9

Patterns of somatic structural variation in human cancer genomes

Li, Yilong; Roberts, Nicola D; Wala, Jeremiah A; Shapira, Ofer; Schumacher, Steven E; Kumar, Kiran; Khurana, Ekta; Waszak, Sebastian; Korbel, Jan O; Haber, James E; Imielinski, Marcin; Weischenfeldt, Joachim; Beroukhim, Rameen; Campbell, Peter J
A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1-7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions-as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2-7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and-in liver cancer-frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.
PMID: 32025012
ISSN: 1476-4687
CID: 5270242
Nature. 2020:578(7793):122-128.DOI: 10.1038/s41586-019-1907-7

The evolutionary history of 2,658 cancers

Gerstung, Moritz; Jolly, Clemency; Leshchiner, Ignaty; Dentro, Stefan C; Gonzalez, Santiago; Rosebrock, Daniel; Mitchell, Thomas J; Rubanova, Yulia; Anur, Pavana; Yu, Kaixian; Tarabichi, Maxime; Deshwar, Amit; Wintersinger, Jeff; Kleinheinz, Kortine; Vázquez-García, Ignacio; Haase, Kerstin; Jerman, Lara; Sengupta, Subhajit; Macintyre, Geoff; Malikic, Salem; Donmez, Nilgun; Livitz, Dimitri G; Cmero, Marek; Demeulemeester, Jonas; Schumacher, Steven; Fan, Yu; Yao, Xiaotong; Lee, Juhee; Schlesner, Matthias; Boutros, Paul C; Bowtell, David D; Zhu, Hongtu; Getz, Gad; Imielinski, Marcin; Beroukhim, Rameen; Sahinalp, S Cenk; Ji, Yuan; Peifer, Martin; Markowetz, Florian; Mustonen, Ville; Yuan, Ke; Wang, Wenyi; Morris, Quaid D; Spellman, Paul T; Wedge, David C; Van Loo, Peter
Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.
PMID: 32025013
ISSN: 1476-4687
CID: 5270252
Nature. 2020:578(7793):82-93.DOI: 10.1038/s41586-020-1969-6

Pan-cancer analysis of whole genomes

Campbell, Peter J; Getz, Gad; Korbel, Jan O; Stuart, Joshua M; Jennings, Jennifer L; Stein, Lincoln D; Perry, Marc D; Nahal-Bose, Hardeep K; Ouellette, B F Francis; Li, Constance H; Rheinbay, Esther; Nielsen, G Petur; Sgroi, Dennis C; Wu, Chin-Lee; Faquin, William C; Deshpande, Vikram; Boutros, Paul C; Lazar, Alexander J; Hoadley, Katherine A; Louis, David N; Dursi, L Jonathan; Yung, Christina K; Bailey, Matthew H; Saksena, Gordon; Raine, Keiran M; Buchhalter, Ivo; Kleinheinz, Kortine; Schlesner, Matthias; Zhang, Junjun; Wang, Wenyi; Wheeler, David A; Ding, Li; Simpson, Jared T; O'Connor, Brian D; Yakneen, Sergei; Ellrott, Kyle; Miyoshi, Naoki; Butler, Adam P; Royo, Romina; Shorser, Solomon I; Vazquez, Miguel; Rausch, Tobias; Tiao, Grace; Waszak, Sebastian M; Rodriguez-Martin, Bernardo; Shringarpure, Suyash; Wu, Dai-Ying; Demidov, German M; Delaneau, Olivier; Hayashi, Shuto; Imoto, Seiya; Habermann, Nina; Segre, Ayellet V; Garrison, Erik; Cafferkey, Andy; Alvarez, Eva G; Heredia-Genestar, José María; Muyas, Francesc; Drechsel, Oliver; Bruzos, Alicia L; Temes, Javier; Zamora, Jorge; Baez-Ortega, Adrian; Kim, Hyung-Lae; Mashl, R Jay; Ye, Kai; DiBiase, Anthony; Huang, Kuan-Lin; Letunic, Ivica; McLellan, Michael D; Newhouse, Steven J; Shmaya, Tal; Kumar, Sushant; Wedge, David C; Wright, Mark H; Yellapantula, Venkata D; Gerstein, Mark; Khurana, Ekta; Marques-Bonet, Tomas; Navarro, Arcadi; Bustamante, Carlos D; Siebert, Reiner; Nakagawa, Hidewaki; Easton, Douglas F; Ossowski, Stephan; Tubio, Jose M C; De La Vega, Francisco M; Estivill, Xavier; Yuen, Denis; Mihaiescu, George L; Omberg, Larsson; Ferretti, Vincent; Sabarinathan, Radhakrishnan; Pich, Oriol; Gonzalez-Perez, Abel; Taylor-Weiner, Amaro; Fittall, Matthew W; Demeulemeester, Jonas; Tarabichi, Maxime; Roberts, Nicola D; Van Loo, Peter; Cortés-Ciriano, Isidro; Urban, Lara; Park, Peter; Zhu, Bin; Pitkänen, Esa; Li, Yilong; Saini, Natalie; Klimczak, Leszek J; Weischenfeldt, Joachim; Sidiropoulos, Nikos; Alexandrov, Ludmil B; Rabionet, Raquel; Escaramis, Georgia; Bosio, Mattia; Holik, Aliaksei Z; Susak, Hana; Prasad, Aparna; Erkek, Serap; Calabrese, Claudia; Raeder, Benjamin; Harrington, Eoghan; Mayes, Simon; Turner, Daniel; Juul, Sissel; Roberts, Steven A; Song, Lei; Koster, Roelof; Mirabello, Lisa; Hua, Xing; Tanskanen, Tomas J; Tojo, Marta; Chen, Jieming; Aaltonen, Lauri A; Rätsch, Gunnar; Schwarz, Roland F; Butte, Atul J; Brazma, Alvis; Chanock, Stephen J; Chatterjee, Nilanjan; Stegle, Oliver; Harismendy, Olivier; Bova, G Steven; Gordenin, Dmitry A; Haan, David; Sieverling, Lina; Feuerbach, Lars; Chalmers, Don; Joly, Yann; Knoppers, Bartha; Molnár-Gábor, Fruzsina; Phillips, Mark; Thorogood, Adrian; Townend, David; Goldman, Mary; Fonseca, Nuno A; Xiang, Qian; Craft, Brian; Piñeiro-Yáñez, Elena; Muñoz, Alfonso; Petryszak, Robert; Füllgrabe, Anja; Al-Shahrour, Fatima; Keays, Maria; Haussler, David; Weinstein, John; Huber, Wolfgang; Valencia, Alfonso; Papatheodorou, Irene; Zhu, Jingchun; Fan, Yu; Torrents, David; Bieg, Matthias; Chen, Ken; Chong, Zechen; Cibulskis, Kristian; Eils, Roland; Fulton, Robert S; Gelpi, Josep L; Gonzalez, Santiago; Gut, Ivo G; Hach, Faraz; Heinold, Michael; Hu, Taobo; Huang, Vincent; Hutter, Barbara; Jäger, Natalie; Jung, Jongsun; Kumar, Yogesh; Lalansingh, Christopher; Leshchiner, Ignaty; Livitz, Dimitri; Ma, Eric Z; Maruvka, Yosef E; Milovanovic, Ana; Nielsen, Morten Muhlig; Paramasivam, Nagarajan; Pedersen, Jakob Skou; Puiggròs, Montserrat; Sahinalp, S Cenk; Sarrafi, Iman; Stewart, Chip; Stobbe, Miranda D; Wala, Jeremiah A; Wang, Jiayin; Wendl, Michael; Werner, Johannes; Wu, Zhenggang; Xue, Hong; Yamaguchi, Takafumi N; Yellapantula, Venkata; Davis-Dusenbery, Brandi N; Grossman, Robert L; Kim, Youngwook; Heinold, Michael C; Hinton, Jonathan; Jones, David R; Menzies, Andrew; Stebbings, Lucy; Hess, Julian M; Rosenberg, Mara; Dunford, Andrew J; Gupta, Manaswi; Imielinski, Marcin; Meyerson, Matthew; Beroukhim, Rameen; Reimand, Jüri; Dhingra, Priyanka; Favero, Francesco; Dentro, Stefan; Wintersinger, Jeff; Rudneva, Vasilisa; Park, Ji Wan; Hong, Eun Pyo; Heo, Seong Gu; Kahles, André; Lehmann, Kjong-Van; Soulette, Cameron M; Shiraishi, Yuichi; Liu, Fenglin; He, Yao; DemircioÄŸlu, Deniz; Davidson, Natalie R; Greger, Liliana; Li, Siliang; Liu, Dongbing; Stark, Stefan G; Zhang, Fan; Amin, Samirkumar B; Bailey, Peter; Chateigner, Aurélien; Frenkel-Morgenstern, Milana; Hou, Yong; Huska, Matthew R; Kilpinen, Helena; Lamaze, Fabien C; Li, Chang; Li, Xiaobo; Li, Xinyue; Liu, Xingmin; Marin, Maximillian G; Markowski, Julia; Nandi, Tannistha; Ojesina, Akinyemi I; Pan-Hammarström, Qiang; Park, Peter J; Pedamallu, Chandra Sekhar; Su, Hong; Tan, Patrick; Teh, Bin Tean; Wang, Jian; Xiong, Heng; Ye, Chen; Yung, Christina; Zhang, Xiuqing; Zheng, Liangtao; Zhu, Shida; Awadalla, Philip; Creighton, Chad J; Wu, Kui; Yang, Huanming; Göke, Jonathan; Zhang, Zemin; Brooks, Angela N; Fittall, Matthew W; Martincorena, Iñigo; Rubio-Perez, Carlota; Juul, Malene; Schumacher, Steven; Shapira, Ofer; Tamborero, David; Mularoni, Loris; Hornshøj, Henrik; Deu-Pons, Jordi; Muiños, Ferran; Bertl, Johanna; Guo, Qianyun; Gonzalez-Perez, Abel; Xiang, Qian; 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; Townend, David; Knoppers, Bartha M; Aminou, Brice; Bartolome, Javier; Boroevich, Keith A; Boyce, Rich; Buchanan, Alex; Byrne, Niall J; Chen, Zhaohong; Cho, Sunghoon; Choi, Wan; Clapham, Peter; Dow, Michelle T; Dursi, Lewis Jonathan; Eils, Juergen; Farcas, Claudiu; Fayzullaev, Nodirjon; Flicek, Paul; Heath, Allison P; Hofmann, Oliver; Hong, Jongwhi H; Hudson, Thomas J; Hübschmann, Daniel; Ivkovic, Sinisa; Jeon, Seung-Hyup; Jiao, Wei; Kabbe, Rolf; Kahles, Andre; Kerssemakers, Jules N A; Kim, Hyunghwan; Kim, Jihoon; Koscher, Michael; Koures, Antonios; Kovacevic, Milena; Lawerenz, Chris; Liu, Jia; Mijalkovic, Sanja; Mijalkovic-Lazic, Ana Mijalkovic; Miyano, Satoru; Nastic, Mia; Nicholson, Jonathan; Ocana, David; Ohi, Kazuhiro; Ohno-Machado, Lucila; Pihl, Todd D; Prinz, Manuel; Radovic, Petar; Short, Charles; Sofia, Heidi J; Spring, Jonathan; Struck, Adam J; Tijanic, Nebojsa; Vicente, David; Wang, Zhining; Williams, Ashley; Woo, Youngchoon; Wright, Adam J; Yang, Liming; Hamilton, Mark P; Johnson, Todd A; Kahraman, Abdullah; Kellis, Manolis; Polak, Paz; Sallari, Richard; Sinnott-Armstrong, Nasa; von Mering, Christian; Beltran, Sergi; Gerhard, Daniela S; Gut, Marta; Trotta, Jean-Rémi; Whalley, Justin P; Niu, Beifang; Espiritu, Shadrielle M G; Gao, Shengjie; Huang, Yi; Lalansingh, Christopher M; Teague, Jon W; Wendl, Michael C; Abascal, Federico; Bader, Gary D; Bandopadhayay, Pratiti; Barenboim, Jonathan; Brunak, Søren; Carlevaro-Fita, Joana; Chakravarty, Dimple; Chan, Calvin Wing Yiu; Choi, Jung Kyoon; Diamanti, Klev; Fink, J Lynn; Frigola, Joan; Gambacorti-Passerini, Carlo; Garsed, Dale W; Haradhvala, Nicholas J; Harmanci, Arif O; Helmy, Mohamed; Herrmann, Carl; Hobolth, Asger; Hodzic, Ermin; Hong, Chen; Isaev, Keren; Izarzugaza, Jose M G; Johnson, Rory; Juul, Randi Istrup; Kim, Jaegil; Kim, Jong K; Jan Komorowski; Lanzós, Andrés; Larsson, Erik; Lee, Donghoon; Li, Shantao; Li, Xiaotong; Lin, Ziao; Liu, Eric Minwei; Lochovsky, Lucas; Lou, Shaoke; Madsen, Tobias; Marchal, Kathleen; Martinez-Fundichely, Alexander; McGillivray, Patrick D; Meyerson, William; Paczkowska, Marta; Park, Keunchil; Park, Kiejung; Pons, Tirso; Pulido-Tamayo, Sergio; Reyes-Salazar, Iker; Reyna, Matthew A; Rubin, Mark A; Salichos, Leonidas; Sander, Chris; Schumacher, Steven E; Shackleton, Mark; Shen, Ciyue; Shrestha, Raunak; Shuai, Shimin; Tsunoda, Tatsuhiko; Umer, Husen M; Uusküla-Reimand, Liis; Verbeke, Lieven P C; Wadelius, Claes; Wadi, Lina; Warrell, Jonathan; Wu, Guanming; Yu, Jun; Zhang, Jing; Zhang, Xuanping; Zhang, Yan; Zhao, Zhongming; Zou, Lihua; Lawrence, Michael S; Raphael, Benjamin J; Bailey, Peter J; Craft, David; Goldman, Mary J; Aburatani, Hiroyuki; Binder, Hans; Dinh, Huy Q; Heath, Simon C; Hoffmann, Steve; Imbusch, Charles David; Kretzmer, Helene; Laird, Peter W; Martin-Subero, Jose I; Nagae, Genta; Shen, Hui; Wang, Qi; Weichenhan, Dieter; Zhou, Wanding; Berman, Benjamin P; Brors, Benedikt; Plass, Christoph; Akdemir, Kadir C; Bowtell, David D L; Burns, Kathleen H; Busanovich, John; Chan, Kin; Dueso-Barroso, Ana; Edwards, Paul A; Etemadmoghadam, Dariush; Haber, James E; Jones, David T W; Ju, Young Seok; Kazanov, Marat D; Koh, Youngil; Kumar, Kiran; Lee, Eunjung Alice; Lee, Jake June-Koo; Lynch, Andy G; Macintyre, Geoff; Markowetz, Florian; Navarro, Fabio C P; Pearson, John V; Rippe, Karsten; Scully, Ralph; Villasante, Izar; Waddell, Nicola; Yang, Lixing; Yao, Xiaotong; Yoon, Sung-Soo; Zhang, Cheng-Zhong; Bergstrom, Erik N; Boot, Arnoud; Covington, Kyle; Fujimoto, Akihiro; Huang, Mi Ni; Islam, S M Ashiqul; McPherson, John R; Morganella, Sandro; Mustonen, Ville; Ng, Alvin Wei Tian; Prokopec, Stephenie D; Vázquez-García, Ignacio; Wu, Yang; Yousif, Fouad; Yu, Willie; Rozen, Steven G; Rudneva, Vasilisa A; Shringarpure, Suyash S; Turner, Daniel J; Xia, Tian; Atwal, Gurnit; Chang, David K; Cooke, Susanna L; Faltas, Bishoy M; Haider, Syed; Kaiser, Vera B; Karlić, Rosa; Kato, Mamoru; Kübler, Kirsten; Margolin, Adam; Martin, Sancha; Nik-Zainal, Serena; P'ng, Christine; Semple, Colin A; Smith, Jaclyn; Sun, Ren X; Thai, Kevin; Wright, Derek W; Yuan, Ke; Biankin, Andrew V; Garraway, Levi; Grimmond, Sean M; Adams, David J; Anur, Pavana; Cao, Shaolong; Christie, Elizabeth L; Cmero, Marek; Cun, Yupeng; Dawson, Kevin J; Dentro, Stefan C; Deshwar, Amit G; Donmez, Nilgun; Drews, Ruben M; Gerstung, Moritz; Ha, Gavin; Haase, Kerstin; Jerman, Lara; Ji, Yuan; Jolly, Clemency; Lee, Juhee; Lee-Six, Henry; Malikic, Salem; Mitchell, Thomas J; Morris, Quaid D; Oesper, Layla; Peifer, Martin; Peto, Myron; Rosebrock, Daniel; Rubanova, Yulia; Salcedo, Adriana; Sengupta, Subhajit; Shi, Ruian; Shin, Seung Jun; Spiro, Oliver; Vembu, Shankar; Wintersinger, Jeffrey A; Yang, Tsun-Po; Yu, Kaixian; Zhu, Hongtu; Spellman, Paul T; Weinstein, John N; Chen, Yiwen; Fujita, Masashi; Han, Leng; Hasegawa, Takanori; Komura, Mitsuhiro; Li, Jun; Mizuno, Shinichi; Shimizu, Eigo; Wang, Yumeng; Xu, Yanxun; Yamaguchi, Rui; Yang, Fan; Yang, Yang; Yoon, Christopher J; Yuan, Yuan; Liang, Han; Alawi, Malik; Borozan, Ivan; Brewer, Daniel S; Cooper, Colin S; Desai, Nikita; Grundhoff, Adam; Iskar, Murat; Su, Xiaoping; Zapatka, Marc; Lichter, Peter; Alsop, Kathryn; Bruxner, Timothy J C; Christ, Angelika N; Cordner, Stephen M; Cowin, Prue A; Drapkin, Ronny; Fereday, Sian; George, Joshy; Hamilton, Anne; Holmes, Oliver; Hung, Jillian A; Kassahn, Karin S; Kazakoff, Stephen H; Kennedy, Catherine J; Leonard, Conrad R; Mileshkin, Linda; Miller, David K; Arnau, Gisela Mir; Mitchell, Chris; Newell, Felicity; Nones, Katia; Patch, Ann-Marie; Quinn, Michael C; Taylor, Darrin F; Thorne, Heather; Traficante, Nadia; Vedururu, Ravikiran; Waddell, Nick M; Waring, Paul M; Wood, Scott; Xu, Qinying; deFazio, Anna; Anderson, Matthew J; Antonello, Davide; Barbour, Andrew P; Bassi, Claudio; Bersani, Samantha; Cataldo, Ivana; Chantrill, Lorraine A; Chiew, Yoke-Eng; Chou, Angela; Cingarlini, Sara; Cloonan, Nicole; Corbo, Vincenzo; Davi, Maria Vittoria; Duthie, Fraser R; Gill, Anthony J; Graham, Janet S; Harliwong, Ivon; Jamieson, Nigel B; Johns, Amber L; Kench, James G; Landoni, Luca; Lawlor, Rita T; Mafficini, Andrea; Merrett, Neil D; Miotto, Marco; Musgrove, Elizabeth A; Nagrial, Adnan M; Oien, Karin A; Pajic, Marina; Pinese, Mark; Robertson, Alan J; Rooman, Ilse; Rusev, Borislav C; Samra, Jaswinder S; Scardoni, Maria; Scarlett, Christopher J; Scarpa, Aldo; Sereni, Elisabetta; Sikora, Katarzyna O; Simbolo, Michele; Taschuk, Morgan L; Toon, Christopher W; Vicentini, Caterina; Wu, Jianmin; Zeps, Nikolajs; Behren, Andreas; Burke, Hazel; Cebon, Jonathan; Dagg, Rebecca A; De Paoli-Iseppi, Ricardo; Dutton-Regester, Ken; Field, Matthew A; Fitzgerald, Anna; Hersey, Peter; Jakrot, Valerie; Johansson, Peter A; Kakavand, Hojabr; Kefford, Richard F; Lau, Loretta M S; Long, Georgina V; Pickett, Hilda A; Pritchard, Antonia L; Pupo, Gulietta M; Saw, Robyn P M; Schramm, Sarah-Jane; Shang, Catherine A; Shang, Ping; Spillane, Andrew J; Stretch, Jonathan R; Tembe, Varsha; Thompson, John F; Vilain, Ricardo E; Wilmott, James S; Yang, Jean Y; Hayward, Nicholas K; Mann, Graham J; Scolyer, Richard A; Bartlett, John; Bavi, Prashant; Chadwick, Dianne E; Chan-Seng-Yue, Michelle; Cleary, Sean; Connor, Ashton A; Czajka, Karolina; Denroche, Robert E; Dhani, Neesha C; Eagles, Jenna; Gallinger, Steven; Grant, Robert C; Hedley, David; Hollingsworth, Michael A; Jang, Gun Ho; Johns, Jeremy; Kalimuthu, Sangeetha; Liang, Sheng-Ben; Lungu, Ilinca; Luo, Xuemei; Mbabaali, Faridah; McPherson, Treasa A; Miller, Jessica K; Moore, Malcolm J; Notta, Faiyaz; Pasternack, Danielle; Petersen, Gloria M; Roehrl, Michael H A; Sam, Michelle; Selander, Iris; Serra, Stefano; Shahabi, Sagedeh; Thayer, Sarah P; Timms, Lee E; Wilson, Gavin W; Wilson, Julie M; Wouters, Bradly G; McPherson, John D; Beck, Timothy A; Bhandari, Vinayak; Collins, Colin C; Fleshner, Neil E; Fox, Natalie S; Fraser, Michael; Heisler, Lawrence E; Lalonde, Emilie; Livingstone, Julie; Meng, Alice; Sabelnykova, Veronica Y; Shiah, Yu-Jia; Van der Kwast, Theodorus; Bristow, Robert G; Ding, Shuai; Fan, Daiming; Li, Lin; Nie, Yongzhan; Xiao, Xiao; Xing, Rui; Yang, Shanlin; Yu, Yingyan; Zhou, Yong; Banks, Rosamonde E; Bourque, Guillaume; Brennan, Paul; Letourneau, Louis; Riazalhosseini, Yasser; Scelo, Ghislaine; Vasudev, Naveen; Viksna, Juris; Lathrop, Mark; Tost, Jörg; Ahn, Sung-Min; Aparicio, Samuel; Arnould, Laurent; Aure, M R; Bhosle, Shriram G; Birney, Ewan; Borg, Ake; Boyault, Sandrine; Brinkman, Arie B; Brock, Jane E; Broeks, Annegien; Børresen-Dale, Anne-Lise; Caldas, Carlos; Chin, Suet-Feung; Davies, Helen; Desmedt, Christine; Dirix, Luc; Dronov, Serge; Ehinger, Anna; Eyfjord, Jorunn E; Fatima, Aquila; Foekens, John A; Futreal, P Andrew; Garred, Øystein; Giri, Dilip D; Glodzik, Dominik; Grabau, Dorthe; Hilmarsdottir, Holmfridur; Hooijer, Gerrit K; Jacquemier, Jocelyne; Jang, Se Jin; Jonasson, Jon G; Jonkers, Jos; Kim, Hyung-Yong; King, Tari A; Knappskog, Stian; Kong, Gu; Krishnamurthy, Savitri; Lakhani, Sunil R; Langerød, Anita; Larsimont, Denis; Lee, Hee Jin; Lee, Jeong-Yeon; Lee, Ming Ta Michael; Lingjærde, Ole Christian; MacGrogan, Gaetan; Martens, John W M; O'Meara, Sarah; Pauporté, Iris; Pinder, Sarah; Pivot, Xavier; Provenzano, Elena; Purdie, Colin A; Ramakrishna, Manasa; Ramakrishnan, Kamna; Reis-Filho, Jorge; Richardson, Andrea L; Ringnér, Markus; Rodriguez, Javier Bartolomé; Rodríguez-González, F Germán; Romieu, Gilles; Salgado, Roberto; Sauer, Torill; Shepherd, Rebecca; Sieuwerts, Anieta M; Simpson, Peter T; Smid, Marcel; Sotiriou, Christos; Span, Paul N; Stefánsson, Ólafur Andri; Stenhouse, Alasdair; Stunnenberg, Henk G; Sweep, Fred; Tan, Benita Kiat Tee; Thomas, Gilles; Thompson, Alastair M; Tommasi, Stefania; Treilleux, Isabelle; Tutt, Andrew; Ueno, Naoto T; Van Laere, Steven; Van den Eynden, Gert G; Vermeulen, Peter; Viari, Alain; Vincent-Salomon, Anne; Wong, Bernice H; Yates, Lucy; Zou, Xueqing; van Deurzen, Carolien H M; van de Vijver, Marc J; Van't Veer, Laura; Ammerpohl, Ole; Aukema, Sietse; Bergmann, Anke K; Bernhart, Stephan H; Borkhardt, Arndt; Borst, Christoph; Burkhardt, Birgit; Claviez, Alexander; Goebler, Maria Elisabeth; Haake, Andrea; Haas, Siegfried; Hansmann, Martin; Hoell, Jessica I; Hummel, Michael; Karsch, Dennis; Klapper, Wolfram; Kneba, Michael; Kreuz, Markus; Kube, Dieter; Küppers, Ralf; Lenze, Dido; Loeffler, Markus; López, Cristina; Mantovani-Löffler, Luisa; Möller, Peter; Ott, German; Radlwimmer, Bernhard; Richter, Julia; Rohde, Marius; Rosenstiel, Philip C; Rosenwald, Andreas; Schilhabel, Markus B; Schreiber, Stefan; Stadler, Peter F; Staib, Peter; Stilgenbauer, Stephan; Sungalee, Stephanie; Szczepanowski, Monika; Toprak, Umut H; Trümper, Lorenz H P; Wagener, Rabea; Zenz, Thorsten; Hovestadt, Volker; von Kalle, Christof; Kool, Marcel; Korshunov, Andrey; Landgraf, Pablo; Lehrach, Hans; Northcott, Paul A; Pfister, Stefan M; Reifenberger, Guido; Warnatz, Hans-Jörg; Wolf, Stephan; Yaspo, Marie-Laure; Assenov, Yassen; Gerhauser, Clarissa; Minner, Sarah; Schlomm, Thorsten; Simon, Ronald; Sauter, Guido; Sültmann, Holger; Biswas, Nidhan K; Maitra, Arindam; Majumder, Partha P; Sarin, Rajiv; Barbi, Stefano; Bonizzato, Giada; Cantù, Cinzia; Dei Tos, Angelo P; Fassan, Matteo; Grimaldi, Sonia; Luchini, Claudio; Malleo, Giuseppe; Marchegiani, Giovanni; Milella, Michele; Paiella, Salvatore; Pea, Antonio; Pederzoli, Paolo; Ruzzenente, Andrea; Salvia, Roberto; Sperandio, Nicola; Arai, Yasuhito; Hama, Natsuko; Hiraoka, Nobuyoshi; Hosoda, Fumie; Nakamura, Hiromi; Ojima, Hidenori; Okusaka, Takuji; Totoki, Yasushi; Urushidate, Tomoko; Fukayama, Masashi; Ishikawa, Shumpei; Katai, Hitoshi; Katoh, Hiroto; Komura, Daisuke; Rokutan, Hirofumi; Saito-Adachi, Mihoko; Suzuki, Akihiro; Taniguchi, Hirokazu; Tatsuno, Kenji; Ushiku, Tetsuo; Yachida, Shinichi; Yamamoto, Shogo; Aikata, Hiroshi; Arihiro, Koji; Ariizumi, Shun-Ichi; Chayama, Kazuaki; Furuta, Mayuko; Gotoh, Kunihito; Hayami, Shinya; Hirano, Satoshi; Kawakami, Yoshiiku; Maejima, Kazuhiro; Nakamura, Toru; Nakano, Kaoru; Ohdan, Hideki; Sasaki-Oku, Aya; Tanaka, Hiroko; Ueno, Masaki; Yamamoto, Masakazu; Yamaue, Hiroki; Choo, Su Pin; Cutcutache, Ioana; Khuntikeo, Narong; Ong, Choon Kiat; Pairojkul, Chawalit; Popescu, Irinel; Ahn, Keun Soo; Aymerich, Marta; Lopez-Guillermo, Armando; López-Otín, Carlos; Puente, Xose S; Campo, Elias; Amary, Fernanda; Baumhoer, Daniel; Behjati, Sam; Bjerkehagen, Bodil; Futreal, P A; Myklebost, Ola; Pillay, Nischalan; Tarpey, Patrick; Tirabosco, Roberto; Zaikova, Olga; Flanagan, Adrienne M; Boultwood, Jacqueline; Bowen, David T; Cazzola, Mario; Green, Anthony R; Hellstrom-Lindberg, Eva; Malcovati, Luca; Nangalia, Jyoti; Papaemmanuil, Elli; Vyas, Paresh; Ang, Yeng; Barr, Hugh; Beardsmore, Duncan; Eldridge, Matthew; Gossage, James; Grehan, Nicola; Hanna, George B; Hayes, Stephen J; Hupp, Ted R; Khoo, David; Lagergren, Jesper; Lovat, Laurence B; MacRae, Shona; O'Donovan, Maria; O'Neill, J Robert; Parsons, Simon L; Preston, Shaun R; Puig, Sonia; Roques, Tom; Sanders, Grant; Sothi, Sharmila; Tavaré, Simon; Tucker, Olga; Turkington, Richard; Underwood, Timothy J; Welch, Ian; Fitzgerald, Rebecca C; Berney, Daniel M; De Bono, Johann S; Cahill, Declan; Camacho, Niedzica; Dennis, Nening M; Dudderidge, Tim; Edwards, Sandra E; Fisher, Cyril; Foster, Christopher S; Ghori, Mohammed; Gill, Pelvender; Gnanapragasam, Vincent J; Gundem, Gunes; Hamdy, Freddie C; Hawkins, Steve; Hazell, Steven; Howat, William; Isaacs, William B; Karaszi, Katalin; Kay, Jonathan D; Khoo, Vincent; Kote-Jarai, Zsofia; Kremeyer, Barbara; Kumar, Pardeep; Lambert, Adam; Leongamornlert, Daniel A; Livni, Naomi; Lu, Yong-Jie; Luxton, Hayley J; Marsden, Luke; Massie, Charlie E; Matthews, Lucy; Mayer, Erik; McDermott, Ultan; Merson, Sue; Neal, David E; Ng, Anthony; Nicol, David; Ogden, Christopher; Rowe, Edward W; Shah, Nimish C; Thomas, Sarah; Thompson, Alan; Verrill, Clare; Visakorpi, Tapio; Warren, Anne Y; Whitaker, Hayley C; Zhang, Hongwei; van As, Nicholas; Eeles, Rosalind A; Abeshouse, Adam; Agrawal, Nishant; Akbani, Rehan; Al-Ahmadie, Hikmat; Albert, Monique; Aldape, Kenneth; Ally, Adrian; Appelbaum, Elizabeth L; Armenia, Joshua; Asa, Sylvia; Auman, J Todd; Balasundaram, Miruna; Balu, Saianand; Barnholtz-Sloan, Jill; Bathe, Oliver F; Baylin, Stephen B; Benz, Christopher; Berchuck, Andrew; Berrios, Mario; Bigner, Darell; Birrer, Michael; Bodenheimer, Tom; Boice, Lori; Bootwalla, Moiz S; Bosenberg, Marcus; Bowlby, Reanne; Boyd, Jeffrey; Broaddus, Russell R; Brock, Malcolm; Brooks, Denise; Bullman, Susan; Caesar-Johnson, Samantha J; Carey, Thomas E; Carlsen, Rebecca; Cerfolio, Robert; Chandan, Vishal S; Chen, Hsiao-Wei; Cherniack, Andrew D; Chien, Jeremy; Cho, Juok; Chuah, Eric; Cibulskis, Carrie; Cope, Leslie; Cordes, Matthew G; Curley, Erin; Czerniak, Bogdan; Danilova, Ludmila; Davis, Ian J; Defreitas, Timothy; Demchok, John A; Dhalla, Noreen; Dhir, Rajiv; Doddapaneni, HarshaVardhan; El-Naggar, Adel; Felau, Ina; Ferguson, Martin L; Finocchiaro, Gaetano; Fong, Kwun M; Frazer, Scott; Friedman, William; Fronick, Catrina C; Fulton, Lucinda A; Gabriel, Stacey B; Gao, Jianjiong; Gehlenborg, Nils; Gershenwald, Jeffrey E; Ghossein, Ronald; Giama, Nasra H; Gibbs, Richard A; Gomez, Carmen; Govindan, Ramaswamy; Hayes, D Neil; Hegde, Apurva M; Heiman, David I; Heins, Zachary; Hepperla, Austin J; Holbrook, Andrea; Holt, Robert A; Hoyle, Alan P; Hruban, Ralph H; Hu, Jianhong; Huang, Mei; Huntsman, David; Huse, Jason; Iacobuzio-Donahue, Christine A; Ittmann, Michael; Jayaseelan, Joy C; Jefferys, Stuart R; Jones, Corbin D; Jones, Steven J M; Juhl, Hartmut; Kang, Koo Jeong; Karlan, Beth; Kasaian, Katayoon; Kebebew, Electron; Kim, Hark Kyun; Korchina, Viktoriya; Kundra, Ritika; Lai, Phillip H; Lander, Eric; Le, Xuan; Lee, Darlene; Levine, Douglas A; Lewis, Lora; Ley, Tim; Li, Haiyan Irene; Lin, Pei; Linehan, W M; Liu, Fei Fei; Lu, Yiling; Lype, Lisa; Ma, Yussanne; Maglinte, Dennis T; Mardis, Elaine R; Marks, Jeffrey; Marra, Marco A; Matthew, Thomas J; Mayo, Michael; McCune, Karen; Meier, Samuel R; Meng, Shaowu; Mieczkowski, Piotr A; Mikkelsen, Tom; Miller, Christopher A; Mills, Gordon B; Moore, Richard A; Morrison, Carl; Mose, Lisle E; Moser, Catherine D; Mungall, Andrew J; Mungall, Karen; Mutch, David; Muzny, Donna M; Myers, Jerome; Newton, Yulia; Noble, Michael S; O'Donnell, Peter; O'Neill, Brian Patrick; Ochoa, Angelica; Park, Joong-Won; Parker, Joel S; Pass, Harvey; Pastore, Alessandro; Pennell, Nathan A; Perou, Charles M; Petrelli, Nicholas; Potapova, Olga; Rader, Janet S; Ramalingam, Suresh; Rathmell, W Kimryn; Reuter, Victor; Reynolds, Sheila M; Ringel, Matthew; Roach, Jeffrey; Roberts, Lewis R; Robertson, A Gordon; Sadeghi, Sara; Saller, Charles; Sanchez-Vega, Francisco; Schadendorf, Dirk; Schein, Jacqueline E; Schmidt, Heather K; Schultz, Nikolaus; Seethala, Raja; Senbabaoglu, Yasin; Shelton, Troy; Shi, Yan; Shih, Juliann; Shmulevich, Ilya; Shriver, Craig; Signoretti, Sabina; Simons, Janae V; Singer, Samuel; Sipahimalani, Payal; Skelly, Tara J; Smith-McCune, Karen; Socci, Nicholas D; Soloway, Matthew G; Sood, Anil K; Tam, Angela; Tan, Donghui; Tarnuzzer, Roy; Thiessen, Nina; Thompson, R Houston; Thorne, Leigh B; Tsao, Ming; Umbricht, Christopher; Van Den Berg, David J; Van Meir, Erwin G; Veluvolu, Umadevi; Voet, Douglas; Wang, Linghua; Weinberger, Paul; Weisenberger, Daniel J; Wigle, Dennis; Wilkerson, Matthew D; Wilson, Richard K; Winterhoff, Boris; Wiznerowicz, Maciej; Wong, Tina; Wong, Winghing; Xi, Liu; Yau, Christina; Zhang, Hailei; Zhang, Hongxin; Zhang, Jiashan
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658Â 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 4-5Â driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10-18.
PMID: 32025007
ISSN: 1476-4687
CID: 5018742
Blood. 2020:136.DOI:

Robust Discovery of Candidate DNA Methylation Cancer Drivers [Meeting Abstract]

Pan, Heng; Renaud, Loic; Chaligne, Ronan; Bloehdorn, Johannes; Tausch, Eugen; Mertens, Daniel; Fink, Anna-Maria; Fischer, Kirsten; Zhang, Chao; Betel, Doron; Gnirke, Andreas; Imielinski, Marcin; Moreaux, Jerome; Hallek, Michael; Meissner, Alexander; Stilgenbauer, Stephan; Wu, Catherine J.; Elemento, Olivier; Landau, Dan A.
ISI:000607205604272
ISSN: 0006-4971
CID: 5270732
Nature. 2019:569(7757):503-508.DOI: 10.1038/s41586-019-1186-3

Next-generation characterization of the Cancer Cell Line Encyclopedia

Ghandi, Mahmoud; Huang, Franklin W; Jané-Valbuena, Judit; Kryukov, Gregory V; Lo, Christopher C; McDonald, E Robert; Barretina, Jordi; Gelfand, Ellen T; Bielski, Craig M; Li, Haoxin; Hu, Kevin; Andreev-Drakhlin, Alexander Y; Kim, Jaegil; Hess, Julian M; Haas, Brian J; Aguet, François; Weir, Barbara A; Rothberg, Michael V; Paolella, Brenton R; Lawrence, Michael S; Akbani, Rehan; Lu, Yiling; Tiv, Hong L; Gokhale, Prafulla C; de Weck, Antoine; Mansour, Ali Amin; Oh, Coyin; Shih, Juliann; Hadi, Kevin; Rosen, Yanay; Bistline, Jonathan; Venkatesan, Kavitha; Reddy, Anupama; Sonkin, Dmitriy; Liu, Manway; Lehar, Joseph; Korn, Joshua M; Porter, Dale A; Jones, Michael D; Golji, Javad; Caponigro, Giordano; Taylor, Jordan E; Dunning, Caitlin M; Creech, Amanda L; Warren, Allison C; McFarland, James M; Zamanighomi, Mahdi; Kauffmann, Audrey; Stransky, Nicolas; Imielinski, Marcin; Maruvka, Yosef E; Cherniack, Andrew D; Tsherniak, Aviad; Vazquez, Francisca; Jaffe, Jacob D; Lane, Andrew A; Weinstock, David M; Johannessen, Cory M; Morrissey, Michael P; Stegmeier, Frank; Schlegel, Robert; Hahn, William C; Getz, Gad; Mills, Gordon B; Boehm, Jesse S; Golub, Todd R; Garraway, Levi A; Sellers, William R
Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource for the acceleration of cancer research using model cancer cell lines.
PMCID:6697103
PMID: 31068700
ISSN: 1476-4687
CID: 5270232