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1,059 results on '"Lawrence, Michael S."'

152. Complementary genomic approaches highlight the P13K/mTOR pathway as a common vulnerability in osteosarcoma

Author

Perry, Jennifer A., Kiezun, Adam, Tonzi, Peter, Van Allen, Eliezer M., Carter, Scott L., Baca, Sylvan C., Cowley, Glenn S., Bhatt, Ami S., Rheinbay, Esther, Pedamallu, Chandra Sekhar, Helman, Elena, Taylor-Weiner, Amaro, McKenna, Aaron, DeLuca, David S., Lawrence, Michael S., Ambrogio, Lauren, Sougnez, Carrie, Sivachenko, Andrey, Walensky, Loren D., Wagle, Nikhil, Mora, Jaume, de Torres, Carmen, Lavarino, Cinzia, Dos Santos Aguiar, Simone, Yunes, Jose Andres, Brandalise, Silvia Regina, Mercado-Celis, Gabriela Elisa, Melendez-Zajgla, Jorge, Cárdenas-Cardós, Rocío, Velasco-Hidalgo, Liliana, Roberts, Charles W. M., Garraway, Levi A., Rodriguez-Galindo, Carlos, Gabriel, Stacey B., Lander, Eric S., Golub, Todd R., Orkin, Stuart H., Getz, Gad, and Janeway, Katherine A.

Published
2014

153. Multi-Omics Profiling of Longitudinal Samples Reveals Early Genomic Changes in Follicular Lymphoma

Author

Bai, Baoyan, primary, Wise, Jillian F., additional, Vodák, Daniel, additional, Nakken, Sigve, additional, Sharma, Ankush, additional, Blaker, Yngvild Nuvin, additional, Brodtkorb, Marianne, additional, Hilden, Vera, additional, Trøen, Gunhild, additional, Ren, Weicheng, additional, Lorenz, Suzanne, additional, Lawrence, Michael S., additional, Myklebost, Ola, additional, Kimby, Eva, additional, Pan-Hammarstrom, Qiang, additional, Meza-Zepeda, Leonardo, additional, Beiske, Klaus, additional, Smeland, Erlend B., additional, Hovig, Eivind, additional, Lingjærde, Ole Christian, additional, Holte, Harald, additional, and Myklebust, June Helen, additional

Published
2022
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155. Chromatin-bound RB targets promoters, enhancers, and CTCF-bound loci and is redistributed by cell-cycle progression

Author

Sanidas, Ioannis, primary, Lee, Hanjun, additional, Rumde, Purva H., additional, Boulay, Gaylor, additional, Morris, Robert, additional, Golczer, Gabriel, additional, Stanzione, Marcello, additional, Hajizadeh, Soroush, additional, Zhong, Jun, additional, Ryan, Meagan B., additional, Corcoran, Ryan B., additional, Drapkin, Benjamin J., additional, Rivera, Miguel N., additional, Dyson, Nicholas J., additional, and Lawrence, Michael S., additional

Published
2022
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156. Abstract 657: Impact of therapy induced APOBEC3A mutagenesis on tumor evolution in non small cell lung cancer

Author

Isozaki, Hideko, primary, Abbasi, Ammal, additional, Nikpour, Naveed, additional, Stanzione, Marcello, additional, Sakhtemani, Ramin, additional, Monroe, Susanna L., additional, Shaw, Alice T., additional, Lin, Jessica J., additional, Sequist, Lecia V., additional, Piotrowska, Zofia, additional, Buisson, Rémi, additional, Lawrence, Michael S., additional, and Hata, Aaron N., additional

Published
2022
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157. YAP1 maintains active chromatin state in head and neck squamous cell carcinomas that promotes tumorigenesis through cooperation with BRD4

Author

Chen, Nana, primary, Golczer, Gabriel, additional, Ghose, Subhoshree, additional, Lin, Brian, additional, Langenbucher, Adam, additional, Webb, Jason, additional, Bhanot, Haymanti, additional, Abt, Nicholas B., additional, Lin, Derrick, additional, Varvares, Mark, additional, Sattler, Martin, additional, Egloff, Ann Marie, additional, Joh, Richard, additional, Uppaluri, Ravindra, additional, Emerick, Kevin S., additional, Lawrence, Michael S., additional, and Saladi, Srinivas Vinod, additional

Published
2022
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158. Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1

Author

Ramkissoon, Lori A., Horowitz, Peleg M., Craig, Justin M., Ramkissoon, Shakti H., Rich, Benjamin E., Schumacher, Steven E., McKenna, Aaron, Lawrence, Michael S., Bergthold, Guillaume, Brastianos, Priscilla K., Tabak, Barbara, Ducar, Matthew D., Van Hummelen, Paul, MacConaill, Laura E., Pouissant-Young, Tina, Cho, Yoon-Jae, Taha, Hala, Mahmoud, Madeha, Bowers, Daniel C., Margraf, Linda, Tabori, Uri, Hawkins, Cynthia, Packer, Roger J., Hill, D. Ashley, Pomeroy, Scott L., Eberhart, Charles G., Dunn, Ian F., Goumnerova, Liliana, Getz, Gad, Chan, Jennifer A., Santagata, Sandro, Hahn, William C., Stiles, Charles D., Ligon, Azra H., Kieran, Mark W., Beroukhim, Rameen, and Ligon, Keith L.

Published
2013

159. Pathway and network analysis of more than 2500 whole cancer genomes

Author

Reyna, Matthew A., Haan, David, Paczkowska, Marta, Verbeke, Lieven P. C., 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 M. G., Khurana, Ekta, Marchal, Kathleen, von Mering, Christian, Sahinalp, S. Cenk, Valencia, Alfonso, Reimand, Jüri, Stuart, Joshua M., Raphael, Benjamin J., Reyna, Matthew A., Haan, David, Paczkowska, Marta, Verbeke, Lieven P. C., 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 M. G., Khurana, Ekta, Marchal, Kathleen, von Mering, Christian, Sahinalp, S. Cenk, Valencia, Alfonso, Reimand, Jüri, Stuart, Joshua M., and Raphael, Benjamin J.

Abstract

© 2020, The Author(s). 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
2022

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

Author

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, 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, and Getz, Gad

Abstract

AbstractThe 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.

Published
2022

161. Integrated genomic characterization of oesophageal carcinoma

Author

Kim, Jihun, Bowlby, Reanne, Mungall, Andrew J., Robertson, Gordon A., Odze, Robert D., Cherniack, Andrew D., Shih, Juliann, Pedamallu, Chandra Sekhar, Cibulskis, Carrie, Dunford, Andrew, Meier, Samuel R., Kim, Jaegil, Raphael, Benjamin J., Wu, Hsin-Ta, Wong, Alexandra M., Willis, Joseph E., Bass, Adam J., Derks, Sarah, Garman, Katherine, McCall, Shannon J., Wiznerowicz, Maciej, Pantazi, Angeliki, Parfenov, Michael, Thorsson, Vésteinn, Shmulevich, Ilya, Dhankani, Varsha, Miller, Michael, Sakai, Ryo, Wang, Kenneth, Schultz, Nikolaus, Shen, Ronglai, Arora, Arshi, Weinhold, Nils, Sánchez-Vega, Francisco, Kelsen, David P., Zhang, Julia, Felau, Ina, Demchok, John, Rabkin, Charles S., Camargo, Constanza M., Zenklusen, Jean Claude, Bowen, Jay, Leraas, Kristen, Lichtenberg, Tara M., Curtis, Christina, Seoane, Jose A., Ojesina, Akinyemi I., Beer, David G., Gulley, Margaret L., Pennathur, Arjun, Luketich, James D., Zhou, Zhongren, Weisenberger, Daniel J., Akbani, Rehan, Lee, Ju-Seog, Liu, Wenbin, Mills, Gordon B., Zhang, Wei, Reid, Brian J, Hinoue, Toshinori, Laird, Peter W., Shen, Hui, Piazuelo, Blanca M., Schneider, Barbara G., McLellan, Michael, Taylor-Weiner, Amaro, Cibulskis, Carrie, Lawrence, Michael, Cibulskis, Kristian, Stewart, Chip, Getz, Gad, Lander, Eric, Gabriel, Stacey B., Ding, Li, McLellan, Michael D., Miller, Christopher A., Appelbaum, Elizabeth L., Cordes, Matthew G., Fronick, Catrina C., Fulton, Lucinda A., Mardis, Elaine R., Wilson, Richard K., Schmidt, Heather K., Fulton, Robert S., Ally, Adrian, Balasundaram, Miruna, Bowlby, Reanne, Carlsen, Rebecca, Chuah, Eric, Dhalla, Noreen, Holt, Robert A., Jones, Steven J. M., Kasaian, Katayoon, Brooks, Denise, Li, Haiyan I., Ma, Yussanne, Marra, Marco A., Mayo, Michael, Moore, Richard A., Mungall, Andrew J., Mungall, Karen L., Robertson, Gordon A., Schein, Jacqueline E., Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Wong, Tina, Cherniack, Andrew D., Shih, Juliann, Pedamallu, Chandra Sekhar, Beroukhim, Rameen, Bullman, Susan, Cibulskis, Carrie, Murray, Bradley A., Saksena, Gordon, Schumacher, Steven E., Gabriel, Stacey, Meyerson, Matthew, Hadjipanayis, Angela, Kucherlapati, Raju, Pantazi, Angeliki, Parfenov, Michael, Ren, Xiaojia, Park, Peter J., Lee, Semin, Kucherlapati, Melanie, Yang, Lixing, Baylin, Stephen B., Hoadley, Katherine A., Weisenberger, Daniel J., Bootwalla, Moiz S., Lai, Phillip H., Van Den Berg, David J., Berrios, Mario, Holbrook, Andrea, Akbani, Rehan, Hwang, Jun-Eul, Jang, Hee-Jin, Liu, Wenbin, Weinstein, John N., Lee, Ju-Seog, Lu, Yiling, Sohn, Bo Hwa, Mills, Gordon, Seth, Sahil, Protopopov, Alexei, Bristow, Christopher A., Mahadeshwar, Harshad S., Tang, Jiabin, Song, Xingzhi, Zhang, Jianhua, Laird, Peter W., Hinoue, Toshinori, Shen, Hui, Cho, Juok, Defrietas, Timothy, Frazer, Scott, Gehlenborg, Nils, Heiman, David I., Lawrence, Michael S., Lin, Pei, Meier, Samuel R., Noble, Michael S., Voet, Doug, Zhang, Hailei, Kim, Jaegil, Polak, Paz, Saksena, Gordon, Chin, Lynda, Getz, Gad, Wong, Alexandra M., Raphael, Benjamin J., Wu, Hsin-Ta, Lee, Semin, Park, Peter J., Yang, Lixing, Thorsson, Vésteinn, Bernard, Brady, Iype, Lisa, Miller, Michael, Reynolds, Sheila M., Shmulevich, Ilya, Dhankani, Varsha, Abeshouse, Adam, Arora, Arshi, Armenia, Joshua, Kundra, Ritika, Ladanyi, Marc, Lehmann, Kjong-Van, Gao, Jianjiong, Sander, Chris, Schultz, Nikolaus, Sánchez-Vega, Francisco, Shen, Ronglai, Weinhold, Nils, Chakravarty, Debyani, Zhang, Hongxin, Radenbaugh, Amie, Hegde, Apruva, Akbani, Rehan, Liu, Wenbin, Weinstein, John N., Chin, Lynda, Bristow, Christopher A., Lu, Yiling, Penny, Robert, Crain, Daniel, Gardner, Johanna, Curley, Erin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Shelton, Troy, Shelton, Candace, Bowen, Jay, Frick, Jessica, Gastier-Foster, Julie M., Gerken, Mark, Leraas, Kristen M., Lichtenberg, Tara M., Ramirez, Nilsa C., Wise, Lisa, Zmuda, Erik, Tarvin, Katherine, Saller, Charles, Park, Young Soo, Button, Michael, Carvalho, Andre L., Reis, Rui Manuel, Matsushita, Marcus Medeiros, Lucchesi, Fabiano, de Oliveira, Antonio Talvane, Le, Xuan, Paklina, Oxana, Setdikova, Galiya, Lee, Jae-Hyuck, Bennett, Joseph, Iacocca, Mary, Huelsenbeck-Dill, Lori, Potapova, Olga, Voronina, Olga, Liu, Ouida, Fulidou, Victoria, Cates, Crystal, Sharp, Alexis, Behera, Madhusmitara, Force, Seth, Khuri, Fadio, Owonikoko, Taofeek, Pickens, Allan, Ramalingam, Suresh, Sica, Gabriel, Dinjens, Winand, van Nistelrooij, Anna, Wijnhoven, Bas, Sandusky, George, Stepa, Serghei, Crain, Daniel, Paulauskis, Joseph, Penny, Robert, Gardner, Johanna, Mallery, David, Morris, Scott, Shelton, Troy, Shelton, Candace, Curley, Erin, Juhl, Hartmut, Zornig, Carsten, Kwon, Sun Young, Kelsen, David, Kim, Hark Kyun, Bartlett, John, Parfitt, Jeremy, Chetty, Runjan, Darling, Gail, Knox, Jennifer, Wong, Rebecca, El-Zimaity, Haila, Liu, Geoffrey, Boussioutas, Alex, Park, Do Young, Kemp, Rafael, Carlotti, Carlos Gilberto, da Cunha Tirapelli, Daniela Pretti, Saggioro, Fabiano Pinto, Sankarankutty, Ajith Kumar, Noushmehr, Houtan, dos Santos, Jose Sebastião, Trevisan, Felipe Amstalden, Eschbacher, Jennifer, Dubina, Michael, Mozgovoy, Eugene, Carey, Frank, Chalmers, Sally, Forgie, Ian, Godwin, Andrew, Reilly, Colleen, Madan, Rashna, Naima, Zaid, Ferrer-Torres, Daysha, Vinco, Michele, Rathmell, Kimryn W., Dhir, Rajiv, Luketich, James, Pennathur, Arjun, Ajani, Jaffer A., McCall, Shannon J., Janjigian, Yelena, Kelsen, David, Ladanyi, Marc, Tang, Laura, Camargo, Constanza M., Ajani, Jaffer A., Cheong, Jae-Ho, Chudamani, Sudha, Liu, Jai, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Demchok, John A., Felau, Ina, Ferguson, Martin L., Shaw, Kenna R. Mills, Sheth, Margi, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean Claude, Hutter, Carolyn M., Sofia, Heidi J., and Zhang, Jiashan

Published
2017
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162. Cell-of-origin chromatin organization shapes the mutational landscape of cancer

Author

Polak, Paz, Karlic, Rosa, Koren, Amnon, Thurman, Robert, Sandstrom, Richard, Lawrence, Michael S., Reynolds, Alex, Rynes, Eric, Vlahovicek, Kristian, Stamatoyannopoulos, John A., and Sunyaev, Shamil R.

Subjects
Gene mutations -- Research, Chromatin -- Health aspects, Genetic research, Cancer -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Cancer is a disease potentiated by mutations in somatic cells. Cancer mutations are not distributed uniformly along the human genome. Instead, different human genomic regions vary by up to fivefold in the local density of cancer somatic mutations (1), posing a fundamental problem for statistical methods used in cancer genomics. Epigenomic organization has been proposed as a major determinant of the cancer mutational landscape (1-5). However, both somatic mutagenesis and epigenomic features are highly cell-type-specific (6,7). We investigated the distribution of mutations in multiple independent samples of diverse cancer types and compared them to cell-type-specific epigenomic features. Here we show that chromatin accessibility and modification, together with replication timing, explain up to 86% of the variance in mutation rates along cancer genomes. The best predictors of local somatic mutation density are epigenomic features derived from the most likely cell type of origin of the corresponding malignancy. Moreover, we find that cell-of-origin chromatin features are much stronger determinants of cancer mutation profiles than chromatin features of matched cancer cell lines. Furthermore, we show that the cell type of origin of a cancer can be accurately determined based on the distribution of mutations along its genome. Thus, the DNA sequence of a cancer genome encompasses a wealth of information about the identity and epigenomic features of its cell of origin., Recent studies have begun to address the underlying causes of cancer mutational heterogeneity by comparing mutation rate variation to the distribution of sequence features, gene expression and epigenetic marks along [...]

Published
2015

163. Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2

Author

Greulich, Heidi, Kaplan, Bethany, Mertins, Philipp, Chen, Tzu-Hsiu, Tanaka, Kumiko E., Yun, Cai-Hong, Zhang, Xiaohong, Lee, Se-Hoon, Cho, Jeonghee, Ambrogio, Lauren, Liao, Rachel, Imielinski, Marcin, Banerji, Shantanu, Berger, Alice H., Lawrence, Michael S., Zhang, Jinghui, Pho, Nam H., Walker, Sarah R., Winckler, Wendy, Getz, Gad, Frank, David, Hahn, William C., Eck, Michael J., Mani, D. R., Jaffe, Jacob D., Carr, Steven A., Wong, Kwok-Kin, and Meyerson, Matthew

Published
2012

164. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

Author

Lohr, Jens G., Stojanov, Petar, Lawrence, Michael S., Auclair, Daniel, Chapuy, Bjoern, Sougnez, Carrie, Cruz-Gordillo, Peter, Knoechel, Birgit, Asmann, Yan W., Slager, Susan L., Novak, Anne J., Dogan, Ahmet, Ansell, Stephen M., Link, Brian K., Zou, Lihua, Gould, Joshua, Saksena, Gordon, Stransky, Nicolas, Rangel-Escareño, Claudia, Fernandez-Lopez, Juan Carlos, Hidalgo-Miranda, Alfredo, Melendez-Zajgla, Jorge, Hernández-Lemus, Enrique, Schwarz-Cruz y Celis, Angela, Imaz-Rosshandler, Ivan, Ojesina, Akinyemi I., Jung, Joonil, Pedamallu, Chandra S., Lander, Eric S., Habermann, Thomas M., Cerhan, James R., Shipp, Margaret A., Getz, Gad, and Golub, Todd R.

Published
2012

165. Translesion DNA synthesis mediates acquired resistance to olaparib plus temozolomide in small cell lung cancer

Author

Stanzione, Marcello, primary, Zhong, Jun, additional, Wong, Edmond, additional, LaSalle, Thomas J., additional, Wise, Jillian F., additional, Simoneau, Antoine, additional, Myers, David T., additional, Phat, Sarah, additional, Sade-Feldman, Moshe, additional, Lawrence, Michael S., additional, Hadden, M. Kyle, additional, Zou, Lee, additional, Farago, Anna F., additional, Dyson, Nicholas J., additional, and Drapkin, Benjamin J., additional

Published
2022
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168. Differential Kinase Activity Across Prostate Tumor Compartments Defines Sensitivity to Target Inhibition

Author

Karabacak, Nezihi Murat, primary, Zheng, Yu, additional, Dubash, Taronish D., additional, Burr, Risa, additional, Micalizzi, Douglas S., additional, Wittner, Ben S., additional, Lin, Maoxuan, additional, Wiley, Devon F., additional, Comaills, Valentine, additional, Emmons, Erin, additional, Niederhoffer, Kira L., additional, Ho, Uyen, additional, Ukleja, Jacob, additional, Che, Dante, additional, Stowe, Hannah, additional, Nieman, Linda T., additional, Haas, Wilhelm, additional, Stott, Shannon L., additional, Lawrence, Michael S., additional, Ting, David T., additional, Miyamoto, David T., additional, Haber, Daniel A., additional, Toner, Mehmet, additional, and Maheswaran, Shyamala, additional

Published
2022
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169. The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

Author

Stransky, Nicolas, Egloff, Ann Marie, Tward, Aaron D., Kostic, Aleksandar D., Cibulskis, Kristian, Sivachenko, Andrey, Kryukov, Gregory V., Lawrence, Michael S., Sougnez, Carrie, McKenna, Aaron, Shefler, Erica, Ramos, Alex H., Stojanov, Petar, Carter, Scott L., Voet, Douglas, Cortés, Maria L., Auclair, Daniel, Berger, Michael F., Saksena, Gordon, Guiducci, Candace, Onofrio, Robert C., Parkin, Melissa, Romkes, Marjorie, Weissfeld, Joel L., Seethala, Raja R., Wang, Lin, Rangel-Escareño, Claudia, Fernandez-Lopez, Juan Carlos, Hidalgo-Miranda, Alfredo, Melendez-Zajgla, Jorge, Winckler, Wendy, Ardlie, Kristin, Gabriel, Stacey B., Meyerson, Matthew, Lander, Eric S., Getz, Gad, Golub, Todd R., Garraway, Levi A., and Grandis, Jennifer R.

Published
2011
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170. Supplement to: Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas.

Author

Brat, Daniel J, Verhaak, Roel GW, Salama, Sofie R., Cooper, Lee, Aldape, Kenneth D, Yung, Alfred W.K, Akbani, Rehan, Barnholtz-Sloan, Jill S., Berger, Mitchel S., Brennan, Cameron, Bristow, Christopher A., Cherniack, Andrew D., Ciriello, Giovanni, Colen, Rivka, Colman, Howard, Flanders, Adam E., Giannini, Caterina, Grifford, Mia, Huse, Jason T., Iavarone, Antonio, Jain, Rajan, Joseph, Isaac, Kim, Jaegil, Kasaian, Katayoon, Laird, Peter W., Mikkelsen, Tom, Miller, Ryan C., Morozova, Olena, Murray, Bradley A., Noushmehr, Houtan, OʼNeill, Brian Patrick, Pachter, Lior, Parsons, Donald W., Poisson, Laila M., Rheinbay, Esther, Robertson, Gordon A., Sougnez, Carrie, Sulman, Erik P., Vandenberg, Scott R., Van Meir, Erwin G., Vitucci, Mark, Deimling, Andreas von, Yoshihara, Kosuke, Zhang, Hailei, Zheng, Siyuan, Crain, Daniel, Lau, Kevin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Penny, Robert, Shelton, Troy, Sherman, Mark, Yena, Peggy, Black, Aaron, Bowen, Jay, Dicostanzo, Katie, Gastier-Foster, Julie, Leraas, Kristen M., Lichtenberg, Tara M., Pierson, Christopher R., Ramirez, Nilsa C., Taylor, Cynthia, Weaver, Stephanie, Wise, Lisa, Zmuda, Erik, Davidsen, Tanja, Demchok, John A., Eley, Greg, Ferguson, Martin L., Hutter, Carolyn M., Mills Shaw, Kenna R., Ozenberger, Bradley A., Sheth, Margi, Sofia, Heidi J., Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean Claude, Ayala, Brenda, Baboud, Julien, Chudamani, Sudha, Jensen, Mark A., Liu, Jia, Pihl, Todd, Raman, Rohini, Wan, Yunhu, Wu, Ye, Ally, Adrian, Auman, Todd J., Balasundaram, Miruna, Balu, Saianand, Baylin, Stephen B., Beroukhim, Rameen, Bootwalla, Moiz S., Bowlby, Reanne, Brooks, Denise, Butterfield, Yaron, Carlsen, Rebecca, Carter, Scott, Chin, Lynda, Chu, Andy, Chuah, Eric, Cibulskis, Kristian, Clarke, Amanda, Coetzee, Simon G., Dhalla, Noreen, Fennell, Tim, Fisher, Sheila, Gabriel, Stacey, Getz, Gad, Gibbs, Richard, Grimsby, Jonna L., Guin, Ranabir, Hadjipanayis, Angela, Hayes, Neil D., Hinoue, Toshinori, Hoadley, Katherine, Holt, Robert A., Hoyle, Alan P., Huang, Franklin, Jefferys, Stuart R., Jones, Steven, Jones, Corbin D., Kucherlapati, Raju, Lai, Phillip H., Lander, Eric, Lee, Semin, Lichtenstein, Lee, Ma, Yussanne, Maglinte, Dennis T., Mahadeshwar, Harshad S., Marra, Marco A., Mayo, Michael, Meng, Shaowu, Meyerson, Matthew L., Mieczkowski, Piotr A., Moore, Richard A., Mose, Lisle E., Mungall, Andrew J., Pantazi, Angeliki, Parfenov, Michael, Park, Peter J., Parker, Joel S., Perou, Charles M., Protopopov, Alexei, Ren, Xiaojia, Roach, Jeffrey, Rosenberg, Mara, Sabedot, Thaís S., Sadeghi, Sara, Schein, Jacqueline, Schumacher, Steven E., Seidman, Jonathan G., Seth, Sahil, Shen, Hui, Simons, Janae V., Sipahimalani, Payal, Soloway, Matthew G., Song, Xingzhi, Stewart, Chip, Sun, Huandong, Tabak, Barbara, Tam, Angela, Tan, Donghui, Tang, Jiabin, Thiessen, Nina, Triche, Timothy, Jr., Van Den Berg, David J., Veluvolu, Umadevi, Waring, Scot, Weisenberger, Daniel J., Wilkerson, Matthew D., Wong, Tina, Wu, Junyuan, Xi, Liu, Xu, Andrew W., Yang, Lixing, Zack, Travis I., Zhang, Jianhua, Aksoy, Arman B., Arachchi, Harindra, Benz, Chris, Bernard, Brady, Carlin, Daniel, Cho, Juok, DiCara, Daniel, Frazer, Scott, Fuller, Gregory N., Gao, JianJiong, Gehlenborg, Nils, Haussler, David, Heiman, David I., Iype, Lisa, Jacobsen, Anders, Ju, Zhenlin, Katzman, Sol, Kim, Hoon, Knijnenburg, Theo, Kreisberg, Richard Bailey, Lawrence, Michael S., Lee, William, Leinonen, Kalle, Lin, Pei, Ling, Shiyun, Liu, Wenbin, Liu, Yingchun, Liu, Yuexin, Lu, Yiling, Mills, Gordon, Ng, Sam, Noble, Michael S., Paull, Evan, Radenbaugh, Amie J., Rao, Arvind, Reynolds, Sheila, Saksena, Gordon, Sanborn, Zack, Sander, Chris, Schultz, Nikolaus, Senbabaoglu, Yasin, Shen, Ronglai, Shmulevich, Ilya, Sinha, Rileen, Stuart, Josh, Sumer, Onur S., Sun, Yichao, Tasman, Natalie, Taylor, Barry S., Voet, Doug, Weinhold, Nils, Weinstein, John N., Yang, Da, Zhang, Wei, Zou, Lihua, Abel, Ty, Brat, Daniel J., Cohen, Mark L., Eschbacher, Jenny, Hattab, Eyas M., Raghunathan, Aditya, Schniederjan, Matthew J., Aziz, Dina, Barnett, Gene, Barrett, Wendi, Bigner, Darell D., Boice, Lori, Brewer, Cathy, Calatozzolo, Chiara, Carlotti, Carlos Gilberto, Jr, Chan, Timothy A., Cuppini, Lucia, Curley, Erin, Cuzzubbo, Stefania, Devine, Karen, DiMeco, Francesco, Duell, Rebecca, Elder, Bradley J, Fehrenbach, Ashley, Finocchiaro, Gaetano, Friedman, William, Fulop, Jordonna, Gardner, Johanna, Hermes, Beth, Kendler, Ady, Lehman, Norman L., Lipp, Eric, Liu, Ouida, Mandt, Randy, McGraw, Mary, McLendon, Roger, McPherson, Christopher, Neder, Luciano, Nguyen, Phuong, Noss, Ardene, Nunziata, Raffaele, Ostrom, Quinn T., Palmer, Cheryl, Perin, Alessandro, Pollo, Bianca, Potapov, Alexander, Potapova, Olga, Rathmell, Kimryn W., Rotin, Daniil, Scarpace, Lisa, Schilero, Cathy, Senecal, Kelly, Shimmel, Kristen, Shurkhay, Vsevolod, Sifri, Suzanne, Singh, Rosy, Sloan, Andrew E., Smolenski, Kathy, Staugaitis, Susan M., Steele, Ruth, Thorne, Leigh, Tirapelli, Daniela P.C., Vallurupalli, Mahitha, Wang, Yun, Warnick, Ronald, Williams, Felicia, Wolinsky, Yingli, Zhang, Jianan, Bell, Sue, Campos, Benito, Herold-Mende, Christel, Jungk, Christine, and Unterberg, Andreas

Published
2015

171. Therapy-induced APOBEC3A drives evolution of persistent cancer cells

Author

Isozaki, Hideko, Sakhtemani, Ramin, Abbasi, Ammal, Nikpour, Naveed, Stanzione, Marcello, Oh, Sunwoo, Langenbucher, Adam, Monroe, Susanna, Su, Wenjia, Cabanos, Heidie Frisco, Siddiqui, Faria M., Phan, Nicole, Jalili, Pégah, Timonina, Daria, Bilton, Samantha, Gomez-Caraballo, Maria, Archibald, Hannah L., Nangia, Varuna, Dionne, Kristin, Riley, Amanda, Lawlor, Matthew, Banwait, Mandeep Kaur, Cobb, Rosemary G., Zou, Lee, Dyson, Nicholas J., Ott, Christopher J., Benes, Cyril, Getz, Gad, Chan, Chang S., Shaw, Alice T., Gainor, Justin F., Lin, Jessica J., Sequist, Lecia V., Piotrowska, Zofia, Yeap, Beow Y., Engelman, Jeffrey A., Lee, Jake June-Koo, Maruvka, Yosef E., Buisson, Rémi, Lawrence, Michael S., and Hata, Aaron N.

Abstract

Acquired drug resistance to anticancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified1–4, the underlying molecular mechanisms shaping tumour evolution during treatment are incompletely understood. Genomic profiling of patient tumours has implicated apolipoprotein B messenger RNA editing catalytic polypeptide-like (APOBEC) cytidine deaminases in tumour evolution; however, their role during therapy and the development of acquired drug resistance is undefined. Here we report that lung cancer targeted therapies commonly used in the clinic can induce cytidine deaminase APOBEC3A (A3A), leading to sustained mutagenesis in drug-tolerant cancer cells persisting during therapy. Therapy-induced A3A promotes the formation of double-strand DNA breaks, increasing genomic instability in drug-tolerant persisters. Deletion of A3A reduces APOBEC mutations and structural variations in persister cells and delays the development of drug resistance. APOBEC mutational signatures are enriched in tumours from patients with lung cancer who progressed after extended responses to targeted therapies. This study shows that induction of A3A in response to targeted therapies drives evolution of drug-tolerant persister cells, suggesting that suppression of A3A expression or activity may represent a potential therapeutic strategy in the prevention or delay of acquired resistance to lung cancer targeted therapy.

Published
2023
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172. Active RB causes visible changes in nuclear organization

Author

Krishnan, Badri, primary, Yasuhara, Takaaki, additional, Rumde, Purva, additional, Stanzione, Marcello, additional, Lu, Chenyue, additional, Lee, Hanjun, additional, Lawrence, Michael S., additional, Zou, Lee, additional, Nieman, Linda T., additional, Sanidas, Ioannis, additional, and Dyson, Nicholas J., additional

Published
2022
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173. Antibody-Peptide Epitope Conjugates for Personalized Cancer Therapy

Author

Zhang, Songfa, primary, Yan, Chuan, additional, Millar, David G., additional, Yang, Qiqi, additional, Heather, James M., additional, Langenbucher, Adam, additional, Morton, Laura T., additional, Sepulveda, Sean, additional, Alpert, Eric, additional, Whelton, Lauren R., additional, Zarrella, Dominique T., additional, Guo, Mei, additional, Minogue, Eleanor, additional, Lawrence, Michael S., additional, Rueda, Bo R., additional, Spriggs, David R., additional, Lu, Weiguo, additional, Langenau, David M., additional, and Cobbold, Mark, additional

Published
2021
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174. Discovery and saturation analysis of cancer genes across 21 tumour types

Author

Lawrence, Michael S., Stojanov, Petar, Mermel, Craig H., Robinson, James T., Garraway, Levi A., Golub, Todd R., Meyerson, Matthew, Gabriel, Stacey B., Lander, Eric S., and Getz, Gad

Subjects
Oncology, Experimental, Tumors -- Physiological aspects -- Genetic aspects, Cancer -- Genetic aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2-20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 600-5,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics., Comprehensive knowledge of the genes underlying human cancers is a critical foundation for cancer diagnostics, therapeutics, clinical-trial design and selection of rational combination therapies. It is now possible to use [...]

Published
2014
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175. NR4A1 regulates expression of immediate early genes, suppressing replication stress in cancer

Author

Guo, Hongshan, primary, Golczer, Gabriel, additional, Wittner, Ben S., additional, Langenbucher, Adam, additional, Zachariah, Marcus, additional, Dubash, Taronish D., additional, Hong, Xin, additional, Comaills, Valentine, additional, Burr, Risa, additional, Ebright, Richard Y., additional, Horwitz, Elad, additional, Vuille, Joanna A., additional, Hajizadeh, Soroush, additional, Wiley, Devon F., additional, Reeves, Brittany A., additional, Zhang, Jia-min, additional, Niederhoffer, Kira L., additional, Lu, Chenyue, additional, Wesley, Benjamin, additional, Ho, Uyen, additional, Nieman, Linda T., additional, Toner, Mehmet, additional, Vasudevan, Shobha, additional, Zou, Lee, additional, Mostoslavsky, Raul, additional, Maheswaran, Shyamala, additional, Lawrence, Michael S., additional, and Haber, Daniel A., additional

Published
2021
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178. APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma

Author

Faden, Daniel L., primary, Kuhs, Krystle A. Lang, additional, Lin, Maoxuan, additional, Langenbucher, Adam, additional, Pinheiro, Maisa, additional, Yeager, Meredith, additional, Cullen, Michael, additional, Boland, Joseph F., additional, Steinberg, Mia, additional, Bass, Sara, additional, Lewis, James S., additional, Lawrence, Michael S., additional, Ferris, Robert L., additional, and Mirabello, Lisa, additional

Published
2021
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181. Dissection of PIK3CA Aberration for Cervical Adenocarcinoma Outcomes

Author

Chung, Tony K. H., primary, Doran, Graeme, additional, Cheung, Tak-Hong, additional, Yim, So-Fan, additional, Yu, Mei-Yung, additional, Worley, Michael J., additional, Elias, Kevin M., additional, Thorner, Aaron R., additional, Pedamallu, Chandra Sekhar, additional, Ojesina, Akinyemi I., additional, Lau, Kei-Man, additional, Ducar, Matthew D., additional, Wong, Raymond R. Y., additional, Wang, Vivian W., additional, Nag, Anwesha, additional, Wollison, Bruce M., additional, Dalgarno, Audrey, additional, Lee, Jacqueline H. S., additional, Yeung, Suet-Ying, additional, Wong, Lo, additional, Horowitz, Neil S., additional, Davis, Michelle R., additional, Leung, Shuk-On A., additional, Mu, Yi, additional, Mok, Samuel C., additional, Chan, Paul K. S., additional, Lawrence, Michael S., additional, Crum, Christopher P., additional, Chiu, Rossa W. K., additional, Berkowitz, Ross S., additional, and Wong, Yick-Fu, additional

Published
2021
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182. RASAL2 Confers Collateral MEK/EGFR Dependency in Chemoresistant Triple-Negative Breast Cancer

Author

Koh, Siang-Boon, primary, Ross, Kenneth, additional, Isakoff, Steven J., additional, Melkonjan, Nsan, additional, He, Lei, additional, Matissek, Karina J., additional, Schultz, Andrew, additional, Mayer, Erica L., additional, Traina, Tiffany A., additional, Carey, Lisa A., additional, Rugo, Hope S., additional, Liu, Minetta C., additional, Stearns, Vered, additional, Langenbucher, Adam, additional, Saladi, Srinivas Vinod, additional, Ramaswamy, Sridhar, additional, Lawrence, Michael S., additional, and Ellisen, Leif W., additional

Published
2021
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183. An extended APOBEC3A mutation signature in cancer.

Author

Langenbucher, Adam, Langenbucher, Adam, Bowen, Danae, Sakhtemani, Ramin, Bournique, Elodie, Wise, Jillian F, Zou, Lee, Bhagwat, Ashok S, Buisson, Rémi, Lawrence, Michael S, Langenbucher, Adam, Langenbucher, Adam, Bowen, Danae, Sakhtemani, Ramin, Bournique, Elodie, Wise, Jillian F, Zou, Lee, Bhagwat, Ashok S, Buisson, Rémi, and Lawrence, Michael S

Abstract

APOBEC mutagenesis, a major driver of cancer evolution, is known for targeting TpC sites in DNA. Recently, we showed that APOBEC3A (A3A) targets DNA hairpin loops. Here, we show that DNA secondary structure is in fact an orthogonal influence on A3A substrate optimality and, surprisingly, can override the TpC sequence preference. VpC (non-TpC) sites in optimal hairpins can outperform TpC sites as mutational hotspots. This expanded understanding of APOBEC mutagenesis illuminates the genomic Twin Paradox, a puzzling pattern of closely spaced mutation hotspots in cancer genomes, in which one is a canonical TpC site but the other is a VpC site, and double mutants are seen only in trans, suggesting a two-hit driver event. Our results clarify this paradox, revealing that both hotspots in these twins are optimal A3A substrates. Our findings reshape the notion of a mutation signature, highlighting the additive roles played by DNA sequence and DNA structure.

Published
2021

184. A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers

Author

Lee, Ryan S., Stewart, Chip, Carter, Scott L., Ambrogio, Lauren, Cibulskis, Kristian, Sougnez, Carrie, Lawrence, Michael S., Auclair, Daniel, Mora, Jaume, Golub, Todd R., Biegel, Jaclyn A., Getz, Gad, and Roberts, Charles W.M.

Subjects
Pediatrics, Genomics, Cancer -- Genetic aspects, Health care industry
Abstract

Cancer is principally considered a genetic disease, and numerous mutations are thought essential to drive its growth. However, the existence of genomically stable cancers and the emergence of mutations in [...]

Published
2012
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185. Sequence analysis of mutations and translocations across breast cancer subtypes

Author

Banerji, Shantanu, Cibulskis, Kristian, Rangel-Escareno, Claudia, Brown, Kristin K., Carter, Scott L., Frederick, Abbie M., Lawrence, Michael S., Sivachenko, Andrey Y., Sougnez, Carrie, Zou, Lihua, Cortes, Maria L., Fernandez-Lopez, Juan C., Peng, Shouyong, Ardlie, Kristin G., Auclair, Daniel, Bautista-Pina, Veronica, Duke, Fujiko, Francis, Joshua, Jung, Joonil, Maffuz-Aziz, Antonio, Onofrio, Robert C., Parkin, Melissa, Pho, Nam H., Quintanar-Jurado, Valeria, Ramos, Alex H., Rebollar-Vega, Rosa, Rodriguez-Cuevas, Sergio, Romero-Cordoba, Sandra L., Schumacher, Steven E., Stransky, Nicolas, Thompson, Kristin M., Uribe-Figueroa, Laura, Baselga, Jose, Beroukhim, Rameen, Polyak, Kornelia, Sgroi, Dennis C., Richardson, Andrea L., Jimenez-Sanchez, Gerardo, Lander, Eric S., Gabriel, Stacey B., Garraway, Levi A., Golub, Todd R., Melendez-Zajgla, Jorge, Toker, Alex, Getz, Gad, Hidalgo-Miranda, Alfredo, and Meyerson, Matthew

Subjects
Gene mutations -- Research, Exome sequencing -- Research, Translocation (Genetics) -- Research, Cancer -- Genetic aspects, Breast cancer -- Genetic aspects -- Analysis -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Shantanu Banerji [1, 2, 3, 15, 16]; Kristian Cibulskis [1, 16]; Claudia Rangel-Escareno [4, 16]; Kristin K. Brown [5, 16]; Scott L. Carter [1]; Abbie M. Frederick [1]; Michael [...]

Published
2012
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186. Huge whole-genome study of human metastatic cancers

Author

Wise, Jillian F. and Lawrence, Michael S.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A better understanding of the genetic changes that enable cancers to spread is crucial. A comprehensive study of whole-genome sequences from metastatic cancer will help researchers to achieve this goal. Comprehensive analysis of genetic changes across metastatic cancers., Author(s): Jillian F. Wise, Michael S. Lawrence Author Affiliations: Huge whole-genome study of human metastatic cancers The major cause of cancer-related deaths is the spread of cancer cells from their [...]

Published
2019
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187. Comprehensive molecular characterization of urothelial bladder carcinoma

Author

Weinstein, John N., Akbani, Rehan, Broom, Bradley M., Wang, Wenyi, Verhaak, Roeland G. W., McConkey, David, Lerner, Seth, Morgan, Margaret, Creighton, Chad J., Smith, Carolyn, Kwiatkowski, David J., Cherniack, Andrew D., Kim, Jaegil, Pedamallu, Chandra Sekhar, Noble, Michael S., Al-Ahmadie, Hikmat A., Reuter, Victor E., Rosenberg, Jonathan E., Bajorin, Dean F., Bochner, Bernard H., Solit, David B., Koppie, Theresa, Robinson, Brian, Gordenin, Dmitry A., Fargo, David, Klimczak, Leszek J., Roberts, Steven A., Au, Jessie, Laird, Peter W., Hinoue, Toshinori, Schultz, Nikolaus, Ramirez, Ricardo, Hansel, Donna, Hoadley, Katherine A., Kim, William Y., Damrauer, Jeffrey S., Baylin, Stephen B., Mungall, Andrew J., Robertson, Gordon A., Chu., Andy, Sougnez, Carrie, Cibulskis, Kristian, Lichtenstein, Lee, Sivachenko, Andrey, Stewart, Chip, Lawrence, Michael S., Getz, Gad, Lander, Eric, Gabriel., Stacey B., Donehower, Lawrence, Carter, Scott L., Saksena, Gordon, Schumacher, Steven E., Freeman, Samuel S., Jung, Joonil, Bhatt, Ami S., Pugh, Trevor, Beroukhim, Rameen, Gabriel, Stacey B., Meyerson, Matthew, Chu, Andy, Ally, Adrian, Balasundaram, Miruna, Butterfield, Yaron S. N., Dhalla, Noreen, Hirst, Carrie, Holt, Robert A., Jones, Steven J. M., Lee, Darlene, Li, Haiyan I., Marra, Marco A., Mayo, Michael, Moore, Richard A., Schein, Jacqueline E., Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Wong, Tina, Wye, Natasja, Bowlby, Reanne, Chuah, Eric, Guin, Ranabir, Shen, Hui, Bootwalla, Moiz S., Jr, Timothy Triche, Lai, Phillip H., Van Den Berg, David J., Weisenberger, Daniel J., Balu, Saianand, Bodenheimer, Tom, Damrauer Alan P. Hoyle, Jeffrey S., Jefferys, Stuart R., Meng, Shaowu, Mose, Lisle E., Simons, Janae V., Soloway, Mathew G., Wu, Junyuan, Parker, Joel S., Hayes, Neil D., Roach, Jeffrey, Buda, Elizabeth, Jones, Corbin D., Mieczkowski, Piotr A., Tan, Donghui, Veluvolu, Umadevi, Waring, Scot, Auman, Todd J., Perou, Charles M., Wilkerson, Matthew D., Santoso, Netty, Parfenov, Michael, Ren, Xiaojia, Pantazi, Angeliki, Hadjipanayis, Angela, Seidman, Jonathan, Kucherlapati, Raju, Lee, Semin, Yang, Lixing, Park, Peter J., Xu, Andrew Wei, Protopopov, Alexei, Zhang, Jianhua, Bristow, Christopher, Mahadeshwar, Harshad S., Seth, Sahil, Song, Xingzhi, Tang, Jiabin, Zeng, Dong, Chin, Lynda, Guo, Charles, Casasent, Tod D., Liu, Wenbin, Ju, Zhenlin, Motter, Thomas, Peng, Bo, Ryan, Michael, Su, Xiaoping, Yang, Ji-Yeon, Lorenzi, Philip L., Yao, Hui, Zhang, Nianxiang, Zhang, Jiexin, Mills, Gordon B., Cho, Juok, DiCara, Daniel, Frazer, Scott, Gehlenborg, Nils, Heiman, David I., Lin, Pei, Liu, Yingchun, Stojanov, Petar, Voet, Doug, Zhang, Hailei, Zou, Lihua, Bernard, Brady, Kreisberg, Dick, Reynolds, Sheila, Rovira, Hector, Shmulevich, Ilya, Gao, Jianjiong, Jacobsen, Anders, Aksoy, Arman B., Antipin, Yevgeniy, Ciriello, Giovanni, Dresdner, Gideon, Gross, Benjamin, Lee, William, Reva, Boris, Shen, Ronglai, Sinha, Rileen, Sumer, Onur S., Weinhold, Nils, Ladanyi, Marc, Sander, Chris, Benz, Christopher, Carlin, Daniel, Haussler, David, Ng, Sam, Paull, Evan O., Stuart, Joshua, Zhu, Jing, Liu, Yuexin, Zhang, Wei, Taylor, Barry S., Lichtenberg, Tara M., Zmuda, Erik, Barr, Thomas, Black, Aaron D., George, Myra, Hanf, Benjamin, Helsel, Carmen, McAllister, Cynthia, Ramirez, Nilsa C., Tabler, Teresa R., Weaver, Stephanie, Wise, Lisa, Bowen, Jay, Gastier-Foster, Julie M., Jian, Weiguo, Tello, Sebrina, Ittman, Michael, Castro, Patricia, McClenden, Whitney D., Gibbs, Richard, Saller, Charles, Tarvin, Katherine, DiPiero, Jennifer M., Owens, Jennifer, Bollag, Roni, Li, Qiang, Weinberger, Paul, Czerwinski, Christine, Huelsenbeck-Dill, Lori, Iacocca, Mary, Petrelli, Nicholas, Rabeno, Brenda, Swanson, Pat, Shelton, Troy, Curley, Erin, Gardner, Johanna, Mallery, David, Penny, Robert, Van Bang, Nguyen, Thi Hanh, Phan, Kohl, Bernard, Van Le, Xuan, Duc Phu, Bui, Thorp, Richard, Tien, Nguyen Viet, Vinh, Le Quang, Sandusky, George, Burks, Eric, Christ, Kimberly, Gee, Jason, Holway, Antonia, Moinzadeh, Alireza, Sorcini, Andrea, Sullivan, Travis, Garcia-Grossman, Ilana R., Regazzi, Ashley M., Boice, Lori, Rathmell, Wendy Kimryn, Thorne, Leigh, Bastacky, Sheldon, Davies, Benjamin, Dhir, Rajiv, Gingrich, Jeffrey, Hrebinko, Ronald, Maranchie, Jodi, Nelson, Joel, Parwani, Anil, Bshara, Wiam, Gaudioso, Carmelo, Morrison, Carl, Alexopoulou, Vina, Bartlett, John, Engel, Jay, Kodeeswaran, Sugy, Antic, Tatjana, O’Donnell, Peter H., Smith, Norm D., Steinberg, Gary D., Egea, Sophie, Gomez-Fernandez, Carmen, Herbert, Lynn, Jorda, Merce, Soloway, Mark, Beaver, Allison, Carter, Suzie, Kapur, Payal, Lewis, Cheryl, Lotan, Yair, Bondaruk, Jolanta, Czerniak, Bogdan, Skinner, Eila, Aldape, Kenneth, Jensen, Mark A., Kahn, Ari B., Pihl, Todd D., Pot, David A., Srinivasan, Deepak, Wan, Yunhu, Ferguson, Martin L., Zenklusen, Jean Claude, Davidsen, Tanja, Demchok, John A., Mills Shaw, Kenna R., Sheth, Margi, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Hutter, Carolyn, Ozenberger, Bradley A., Sofia, Heidi J., and Eley, Greg

Published
2014
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188. Landscape of genomic alterations in cervical carcinomas

Author

Ojesina, Akinyemi I., Lichtenstein, Lee, Freeman, Samuel S., Pedamallu, Chandra Sekhar, Imaz-Rosshandler, Ivan, Pugh, Trevor J., Cherniack, Andrew D., Ambrogio, Lauren, Cibulskis, Kristian, Bertelsen, Bjørn, Romero-Cordoba, Sandra, Treviño, Victor, Vazquez-Santillan, Karla, Guadarrama, Alberto Salido, Wright, Alexi A., Rosenberg, Mara W., Duke, Fujiko, Kaplan, Bethany, Wang, Rui, Nickerson, Elizabeth, Walline, Heather M., Lawrence, Michael S., Stewart, Chip, Carter, Scott L., McKenna, Aaron, Rodriguez-Sanchez, Iram P., Espinosa-Castilla, Magali, Woie, Kathrine, Bjorge, Line, Wik, Elisabeth, Halle, Mari K., Hoivik, Erling A., Krakstad, Camilla, Gabiño, Nayeli Belem, Gómez-Macías, Gabriela Sofia, Valdez-Chapa, Lezmes D., Garza-Rodríguez, María Lourdes, Maytorena, German, Vazquez, Jorge, Rodea, Carlos, Cravioto, Adrian, Cortes, Maria L., Greulich, Heidi, Crum, Christopher P., Neuberg, Donna S., Hidalgo-Miranda, Alfredo, Escareno, Claudia Rangel, Akslen, Lars A., Carey, Thomas E., Vintermyr, Olav K., Gabriel, Stacey B., Barrera-Saldaña, Hugo A., Melendez-Zajgla, Jorge, Getz, Gad, Salvesen, Helga B., and Meyerson, Matthew

Published
2014
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190. An extended APOBEC3A mutation signature in cancer

Author

Langenbucher, Adam, primary, Bowen, Danae, additional, Sakhtemani, Ramin, additional, Bournique, Elodie, additional, Wise, Jillian F., additional, Zou, Lee, additional, Bhagwat, Ashok S., additional, Buisson, Rémi, additional, and Lawrence, Michael S., additional

Published
2021
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191. Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion–Positive Lung Cancer

Author

Lin, Jessica J., primary, Choudhury, Noura J., additional, Yoda, Satoshi, additional, Zhu, Viola W., additional, Johnson, Ted W., additional, Sakhtemani, Ramin, additional, Dagogo-Jack, Ibiayi, additional, Digumarthy, Subba R., additional, Lee, Charlotte, additional, Do, Andrew, additional, Peterson, Jennifer, additional, Prutisto-Chang, Kylie, additional, Malik, Wafa, additional, Hubbeling, Harper G., additional, Langenbucher, Adam, additional, Schoenfeld, Adam J., additional, Falcon, Christina J., additional, Temel, Jennifer S., additional, Sequist, Lecia V., additional, Yeap, Beow Y., additional, Lennerz, Jochen K., additional, Shaw, Alice T., additional, Lawrence, Michael S., additional, Ou, Sai-Hong Ignatius, additional, Hata, Aaron N., additional, Drilon, Alexander, additional, and Gainor, Justin F., additional

Published
2021
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192. Somatic mutations affect key pathways in lung adenocarcinoma

Author

Ding, Li, Getz, Gad, Wheeler, David A., Mardis, Elaine R., McLellan, Michael D., Cibulskis, Kristian, Sougnez, Carrie, Greulich, Heidi, Muzny, Donna M., Morgan, Margaret B., Fulton, Lucinda, Fulton, Robert S., Zhang, Qunyuan, Wendl, Michael C., Lawrence, Michael S., Larson, David E., Chen, Ken, Dooling, David J., Sabo, Aniko, Hawes, Alicia C., Shen, Hua, Jhangiani, Shalini N., Lewis, Lora R., Hall, Otis, Zhu, Yiming, Mathew, Tittu, Ren, Yanru, Yao, Jiqiang, Scherer, Steven E., Clerc, Kerstin, Metcalf, Ginger A., Ng, Brian, Milosavljevic, Aleksandar, Gonzalez-Garay, Manuel L., Osborne, John R., Meyer, Rick, Shi, Xiaoqi, Tang, Yuzhu, Koboldt, Daniel C., Lin, Ling, Abbott, Rachel, Miner, Tracie L., Pohl, Craig, Fewell, Ginger, Haipek, Carrie, Schmidt, Heather, Dunford-Shore, Brian H., Kraja, Aldi, Crosby, Seth D., Sawyer, Christopher S., Vickery, Tammi, Sander, Sacha, Robinson, Jody, Winckler, Wendy, Baldwin, Jennifer, Chirieac, Lucian R., Dutt, Amit, Fennell, Tim, Hanna, Megan, Johnson, Bruce E., Onofrio, Robert C., Thomas, Roman K., Tonon, Giovanni, Weir, Barbara A., Zhao, Xiaojun, Ziaugra, Liuda, Zody, Michael C., Giordano, Thomas, Orringer, Mark B., Roth, Jack A., Spitz, Margaret R., Wistuba, Ignacio I., Ozenberger, Bradley, Good, Peter J., Chang, Andrew C., Beer, David G., Watson, Mark A., Ladanyi, Marc, Broderick, Stephen, Yoshizawa, Akihiko, Travis, William D., Pao, William, Province, Michael A., Weinstock, George M., Varmus, Harold E., Gabriel, Stacey B., Lander, Eric S., Gibbs, Richard A., Meyerson, Matthew, and Wilson, Richard K.

Subjects
Gene mutations -- Research -- Physiological aspects -- Genetic aspects, Nucleotide sequencing -- Research -- Physiological aspects -- Genetic aspects, Adenocarcinoma -- Genetic aspects -- Research -- Care and treatment -- Prognosis -- Diagnosis, DNA sequencing -- Research -- Physiological aspects -- Genetic aspects, Lung cancer -- Genetic aspects -- Research -- Care and treatment -- Diagnosis -- Prognosis, Environmental issues, Science and technology, Zoology and wildlife conservation, Diagnosis, Care and treatment, Physiological aspects, Genetic aspects, Research, Prognosis
Abstract

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations [...]

Published
2008

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

Author

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 MC, 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, PCAWG Drivers and Functional Interpretation Working Group, PCAWG Structural Variation Working Group, Weischenfeldt, Joachim, Beroukhim, Rameen, Martincorena, Iñigo, Pedersen, Jakob Skou, Getz, Gad, PCAWG Consortium, and Apollo - University of Cambridge Repository

Subjects
Neoplastic, Genome, Genome, Human, General Science & Technology, DNA Breaks, PCAWG Consortium, Gene Expression Regulation, Neoplastic, Databases, PCAWG Drivers and Functional Interpretation Working Group, Gene Expression Regulation, Genetic, INDEL Mutation, Neoplasms, Databases, Genetic, PCAWG Structural Variation Working Group, Mutation, Humans, Human, Genome-Wide Association Study
Abstract

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.

Published
2020

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

Author

Group, PCAWG Drivers, Functional Interpretation Working, Group, PCAWG Structural Variation Working, Consortium, PCAWG, PCAWG Consortium, Rheinbay, Esther, Nielsen, Morten M., Abascal, Federico, Wala, Jeremiah A, Shapira, Ofer, Tiao, Grace, Hornshøj, Henrik, Hess, Julian M, Juul, Randi I., 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, André, Kahraman, Abdullah, Kim, Youngwook, Komorowski, Jan, Kumar, Kiran, Kumar, Sushant, Lee, Donghoon, Lehmann, Kjong-Van, Li, Yilong, Liu, Eric M., 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 S., and Getz, Gad

Subjects
Cancer genomics, Computational biology and bioinformatics
Abstract

The discovery of drivers of cancer has traditionally focused on protein-coding genes14. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658genomes 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 althoughpoint 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., Nature, 578 (7793), ISSN:0028-0836, ISSN:1476-4687

Published
2020
Full Text
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195. Recurrent and functional regulatory mutations in breast cancer

Author

Rheinbay, Esther, Parasuraman, Prasanna, Grimsby, Jonna, Tiao, Grace, Engreitz, Jesse M., Kim, Jaegil, Lawrence, Michael S., Taylor-Weiner, Amaro, Rodriguez-Cuevas, Sergio, Rosenberg, Mara, Hess, Julian, Stewart, Chip, Maruvka, Yosef E., Stojanov, Petar, Cortes, Maria L., Seepo, Sara, Cibulskis, Carrie, Tracy, Adam, Pugh, Trevor J., Lee, Jesse, Zheng, Zongli, Ellisen, Leif W., Iafrate, A. John, Boehm, Jesse S., Gabriel, Stacey B., Meyerson, Matthew, Golub, Todd R., Baselga, Jose, Hidalgo-Miranda, Alfredo, Shioda, Toshi, Bernards, Andre, Lander, Eric S., and Getz, Gad

Subjects
Cancer genetics -- Genetic aspects -- Analysis -- Health aspects -- Research, Cancer research, Tumors -- Genetic aspects, Breast cancer -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients., Author(s): Esther Rheinbay [1, 2]; Prasanna Parasuraman [2]; Jonna Grimsby [1]; Grace Tiao [1]; Jesse M. Engreitz [1, 3]; Jaegil Kim [1]; Michael S. Lawrence [1, 2]; Amaro Taylor-Weiner [1]; [...]

Published
2017
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196. Pathway and network analysis of more than 2500 whole cancer genomes.

Author

Reyna, Matthew A, Haan, David, Paczkowska, Marta, Verbeke, Lieven P C, 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 M G, Khurana, Ekta, Marchal, Kathleen, von Mering, Christian, Sahinalp, S Cenk, Valencia, Alfonso, Reimand, Jüri, Stuart, Joshua M, Raphael, Benjamin J, Wadelius, Claes, Reyna, Matthew A, Haan, David, Paczkowska, Marta, Verbeke, Lieven P C, 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 M G, Khurana, Ekta, Marchal, Kathleen, von Mering, Christian, Sahinalp, S Cenk, Valencia, Alfonso, Reimand, Jüri, Stuart, Joshua M, Raphael, Benjamin J, and Wadelius, Claes

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., CW medlem i PCAWG Consortium.

Published
2020
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197. Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis

Author

Carlevaro-Fita, Joana, Lanzos, Andres, Feuerbach, Lars, Hong, Chen, Mas-Ponte, David, Pedersen, Jakob Skou, Johnson, Rory, Abascal, Federico, Amin, Samirkumar B., Bader, Gary D., Barenboim, Jonathan, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A., Brunak, Soren, Campbell, Peter J., Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, 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, Hornshoj, Henrik, Isaev, Keren, Izarzugaza, Jose M. G., 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, 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, Inigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E., McGillivray, Patrick D., Meyerson, William, Muinos, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pich, Oriol, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J., Reimand, Juri, Reyes-Salazar, Iker, Reyna, Matthew A., Rheinbay, Esther, Rubin, Mark A., Rubio-Perez, Carlota, Sabarinathan, Radhakrishnan, Sahinalp, S. Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D., Stuart, Joshua M., Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen Muhammad, Uuskula-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven P. C., 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, Carlevaro-Fita, Joana, Lanzos, Andres, Feuerbach, Lars, Hong, Chen, Mas-Ponte, David, Pedersen, Jakob Skou, Johnson, Rory, Abascal, Federico, Amin, Samirkumar B., Bader, Gary D., Barenboim, Jonathan, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A., Brunak, Soren, Campbell, Peter J., Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, 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, Hornshoj, Henrik, Isaev, Keren, Izarzugaza, Jose M. G., 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, 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, Inigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E., McGillivray, Patrick D., Meyerson, William, Muinos, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pich, Oriol, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J., Reimand, Juri, Reyes-Salazar, Iker, Reyna, Matthew A., Rheinbay, Esther, Rubin, Mark A., Rubio-Perez, Carlota, Sabarinathan, Radhakrishnan, Sahinalp, S. Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D., Stuart, Joshua M., Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen Muhammad, Uuskula-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven P. C., 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, and von Mering, Christian

Abstract

Joana Carlevaro-Fita, Andres Lanzos et al. present the Cancer LncRNA Census (CLC), a manually curated dataset of 122 long noncoding RNAs (lncRNAs) with experimentally-validated functions in cancer based on data from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. CLC lncRNAs have unique gene features, and a number display evidence for cancer-driving functions that are conserved from humans to mice. Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.

Published
2020
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198. Quantification of ongoing APOBEC3A activity in tumor cells by monitoring RNA editing at hotspots.

Author

Jalili, Pégah, Jalili, Pégah, Bowen, Danae, Langenbucher, Adam, Park, Shinho, Aguirre, Kevin, Corcoran, Ryan B, Fleischman, Angela G, Lawrence, Michael S, Zou, Lee, Buisson, Rémi, Jalili, Pégah, Jalili, Pégah, Bowen, Danae, Langenbucher, Adam, Park, Shinho, Aguirre, Kevin, Corcoran, Ryan B, Fleischman, Angela G, Lawrence, Michael S, Zou, Lee, and Buisson, Rémi

Abstract

APOBEC3A is a cytidine deaminase driving mutagenesis, DNA replication stress and DNA damage in cancer cells. While the APOBEC3A-induced vulnerability of cancers offers an opportunity for therapy, APOBEC3A protein and mRNA are difficult to quantify in tumors due to their low abundance. Here, we describe a quantitative and sensitive assay to measure the ongoing activity of APOBEC3A in tumors. Using hotspot RNA mutations identified from APOBEC3A-positive tumors and droplet digital PCR, we develop an assay to quantify the RNA-editing activity of APOBEC3A. This assay is superior to APOBEC3A protein- and mRNA-based assays in predicting the activity of APOBEC3A on DNA. Importantly, we demonstrate that the RNA mutation-based APOBEC3A assay is applicable to clinical samples from cancer patients. Our study presents a strategy to follow the dysregulation of APOBEC3A in tumors, providing opportunities to investigate the role of APOBEC3A in tumor evolution and to target the APOBEC3A-induced vulnerability in therapy.

Published
2020

199. Pathway and network analysis of more than 2500 whole cancer genomes

Author

Reyna, Matthew A., Haan, David, Paczkowska, Marta, Verbeke, Lieven P.C., 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 M.G., 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, Larsson, Erik, Nielsen, Morten Muhlig, Sidiropoulos, Nikos, Weischenfeldt, Joachim, Reyna, Matthew A., Haan, David, Paczkowska, Marta, Verbeke, Lieven P.C., 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 M.G., 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, Larsson, Erik, Nielsen, Morten Muhlig, Sidiropoulos, Nikos, and Weischenfeldt, Joachim

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
2020

200. 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. 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. 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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. 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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

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