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51. Integrated Genomic Characterization of Papillary Thyroid Carcinoma

Author

Agrawal, Nishant, primary, Akbani, Rehan, additional, Aksoy, B. Arman, additional, Ally, Adrian, additional, Arachchi, Harindra, additional, Asa, Sylvia L., additional, Auman, J. Todd, additional, Balasundaram, Miruna, additional, Balu, Saianand, additional, Baylin, Stephen B., additional, Behera, Madhusmita, additional, Bernard, Brady, additional, Beroukhim, Rameen, additional, Bishop, Justin A., additional, Black, Aaron D., additional, Bodenheimer, Tom, additional, Boice, Lori, additional, Bootwalla, Moiz S., additional, Bowen, Jay, additional, Bowlby, Reanne, additional, Bristow, Christopher A., additional, Brookens, Robin, additional, Brooks, Denise, additional, Bryant, Robert, additional, Buda, Elizabeth, additional, Butterfield, Yaron S.N., additional, Carling, Tobias, additional, Carlsen, Rebecca, additional, Carter, Scott L., additional, Carty, Sally E., additional, Chan, Timothy A., additional, Chen, Amy Y., additional, Cherniack, Andrew D., additional, Cheung, Dorothy, additional, Chin, Lynda, additional, Cho, Juok, additional, Chu, Andy, additional, Chuah, Eric, additional, Cibulskis, Kristian, additional, Ciriello, Giovanni, additional, Clarke, Amanda, additional, Clayman, Gary L., additional, Cope, Leslie, additional, Copland, John A., additional, Covington, Kyle, additional, Danilova, Ludmila, additional, Davidsen, Tanja, additional, Demchok, John A., additional, DiCara, Daniel, additional, Dhalla, Noreen, additional, Dhir, Rajiv, additional, Dookran, Sheliann S., additional, Dresdner, Gideon, additional, Eldridge, Jonathan, additional, Eley, Greg, additional, El-Naggar, Adel K., additional, Eng, Stephanie, additional, Fagin, James A., additional, Fennell, Timothy, additional, Ferris, Robert L., additional, Fisher, Sheila, additional, Frazer, Scott, additional, Frick, Jessica, additional, Gabriel, Stacey B., additional, Ganly, Ian, additional, Gao, Jianjiong, additional, Garraway, Levi A., additional, Gastier-Foster, Julie M., additional, Getz, Gad, additional, Gehlenborg, Nils, additional, Ghossein, Ronald, additional, Gibbs, Richard A., additional, Giordano, Thomas J., additional, Gomez-Hernandez, Karen, additional, Grimsby, Jonna, additional, Gross, Benjamin, additional, Guin, Ranabir, additional, Hadjipanayis, Angela, additional, Harper, Hollie A., additional, Hayes, D. Neil, additional, Heiman, David I., additional, Herman, James G., additional, Hoadley, Katherine A., additional, Hofree, Matan, additional, Holt, Robert A., additional, Hoyle, Alan P., additional, Huang, Franklin W., additional, Huang, Mei, additional, Hutter, Carolyn M., additional, Ideker, Trey, additional, Iype, Lisa, additional, Jacobsen, Anders, additional, Jefferys, Stuart R., additional, Jones, Corbin D., additional, Jones, Steven J.M., additional, Kasaian, Katayoon, additional, Kebebew, Electron, additional, Khuri, Fadlo R., additional, Kim, Jaegil, additional, Kramer, Roger, additional, Kreisberg, Richard, additional, Kucherlapati, Raju, additional, Kwiatkowski, David J., additional, Ladanyi, Marc, additional, Lai, Phillip H., additional, Laird, Peter W., additional, Lander, Eric, additional, Lawrence, Michael S., additional, Lee, Darlene, additional, Lee, Eunjung, additional, Lee, Semin, additional, Lee, William, additional, Leraas, Kristen M., additional, Lichtenberg, Tara M., additional, Lichtenstein, Lee, additional, Lin, Pei, additional, Ling, Shiyun, additional, Liu, Jinze, additional, Liu, Wenbin, additional, Liu, Yingchun, additional, LiVolsi, Virginia A., additional, Lu, Yiling, additional, Ma, Yussanne, additional, Mahadeshwar, Harshad S., additional, Marra, Marco A., additional, Mayo, Michael, additional, McFadden, David G., additional, Meng, Shaowu, additional, Meyerson, Matthew, additional, Mieczkowski, Piotr A., additional, Miller, Michael, additional, Mills, Gordon, additional, Moore, Richard A., additional, Mose, Lisle E., additional, Mungall, Andrew J., additional, Murray, Bradley A., additional, Nikiforov, Yuri E., additional, Noble, Michael S., additional, Ojesina, Akinyemi I., additional, Owonikoko, Taofeek K., additional, Ozenberger, Bradley A., additional, Pantazi, Angeliki, additional, Parfenov, Michael, additional, Park, Peter J., additional, Parker, Joel S., additional, Paull, Evan O., additional, Pedamallu, Chandra Sekhar, additional, Perou, Charles M., additional, Prins, Jan F., additional, Protopopov, Alexei, additional, Ramalingam, Suresh S., additional, Ramirez, Nilsa C., additional, Ramirez, Ricardo, additional, Raphael, Benjamin J., additional, Rathmell, W. Kimryn, additional, Ren, Xiaojia, additional, Reynolds, Sheila M., additional, Rheinbay, Esther, additional, Ringel, Matthew D., additional, Rivera, Michael, additional, Roach, Jeffrey, additional, Robertson, A. Gordon, additional, Rosenberg, Mara W., additional, Rosenthal, Matthew, additional, Sadeghi, Sara, additional, Saksena, Gordon, additional, Sander, Chris, additional, Santoso, Netty, additional, Schein, Jacqueline E., additional, Schultz, Nikolaus, additional, Schumacher, Steven E., additional, Seethala, Raja R., additional, Seidman, Jonathan, additional, Senbabaoglu, Yasin, additional, Seth, Sahil, additional, Sharpe, Samantha, additional, Shaw, Kenna R. Mills, additional, Shen, John P., additional, Shen, Ronglai, additional, Sherman, Steven, additional, Sheth, Margi, additional, Shi, Yan, additional, Shmulevich, Ilya, additional, Sica, Gabriel L., additional, Simons, Janae V., additional, Sinha, Rileen, additional, Sipahimalani, Payal, additional, Smallridge, Robert C., additional, Sofia, Heidi J., additional, Soloway, Matthew G., additional, Song, Xingzhi, additional, Sougnez, Carrie, additional, Stewart, Chip, additional, Stojanov, Petar, additional, Stuart, Joshua M., additional, Sumer, S. Onur, additional, Sun, Yichao, additional, Tabak, Barbara, additional, Tam, Angela, additional, Tan, Donghui, additional, Tang, Jiabin, additional, Tarnuzzer, Roy, additional, Taylor, Barry S., additional, Thiessen, Nina, additional, Thorne, Leigh, additional, Thorsson, Vésteinn, additional, Tuttle, R. Michael, additional, Umbricht, Christopher B., additional, Van Den Berg, David J., additional, Vandin, Fabio, additional, Veluvolu, Umadevi, additional, Verhaak, Roel G.W., additional, Vinco, Michelle, additional, Voet, Doug, additional, Walter, Vonn, additional, Wang, Zhining, additional, Waring, Scot, additional, Weinberger, Paul M., additional, Weinhold, Nils, additional, Weinstein, John N., additional, Weisenberger, Daniel J., additional, Wheeler, David, additional, Wilkerson, Matthew D., additional, Wilson, Jocelyn, additional, Williams, Michelle, additional, Winer, Daniel A., additional, Wise, Lisa, additional, Wu, Junyuan, additional, Xi, Liu, additional, Xu, Andrew W., additional, Yang, Liming, additional, Yang, Lixing, additional, Zack, Travis I., additional, Zeiger, Martha A., additional, Zeng, Dong, additional, Zenklusen, Jean Claude, additional, Zhao, Ni, additional, Zhang, Hailei, additional, Zhang, Jianhua, additional, Zhang, Jiashan (Julia), additional, Zhang, Wei, additional, Zmuda, Erik, additional, and Zou, Lihua, additional

Published
2014
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52. The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

Author

Davis, Caleb F., primary, Ricketts, Christopher J., additional, Wang, Min, additional, Yang, Lixing, additional, Cherniack, Andrew D., additional, Shen, Hui, additional, Buhay, Christian, additional, Kang, Hyojin, additional, Kim, Sang Cheol, additional, Fahey, Catherine C., additional, Hacker, Kathryn E., additional, Bhanot, Gyan, additional, Gordenin, Dmitry A., additional, Chu, Andy, additional, Gunaratne, Preethi H., additional, Biehl, Michael, additional, Seth, Sahil, additional, Kaipparettu, Benny A., additional, Bristow, Christopher A., additional, Donehower, Lawrence A., additional, Wallen, Eric M., additional, Smith, Angela B., additional, Tickoo, Satish K., additional, Tamboli, Pheroze, additional, Reuter, Victor, additional, Schmidt, Laura S., additional, Hsieh, James J., additional, Choueiri, Toni K., additional, Hakimi, A. Ari, additional, Chin, Lynda, additional, Meyerson, Matthew, additional, Kucherlapati, Raju, additional, Park, Woong-Yang, additional, Robertson, A. Gordon, additional, Laird, Peter W., additional, Henske, Elizabeth P., additional, Kwiatkowski, David J., additional, Park, Peter J., additional, Morgan, Margaret, additional, Shuch, Brian, additional, Muzny, Donna, additional, Wheeler, David A., additional, Linehan, W. Marston, additional, Gibbs, Richard A., additional, Rathmell, W. Kimryn, additional, Creighton, Chad J., additional, Creighton, Chad J., additional, Davis, Caleb F., additional, Wheeler, David A., additional, Gibbs, Richard A., additional, Signoretti, Sabina, additional, Robertson, A. Gordon, additional, Henske, Elizabeth P., additional, Kwiatkowski, David J., additional, Ricketts, Christopher, additional, Linehan, W. Marston, additional, Seiler, Michael, additional, Rathmell, W. Kimryn, additional, Laird, Peter W., additional, Chao, Hsu, additional, Dahdouli, Mike, additional, Xi, Liu, additional, Kakkar, Nipun, additional, Reid, Jeffrey G., additional, Downs, Brittany, additional, Drummond, Jennifer, additional, Morton, Donna, additional, Doddapaneni, Harsha, additional, Lewis, Lora, additional, English, Adam, additional, Meng, Qingchang, additional, Kovar, Christie, additional, Wang, Qiaoyan, additional, Hale, Walker, additional, Hawes, Alicia, additional, Kalra, Divya, additional, Walker, Kimberly, additional, Murray, Bradley A., additional, Sougnez, Carrie, additional, Saksena, Gordon, additional, Carter, Scott L., additional, Schumacher, Steven E., additional, Tabak, Barbara, additional, Zack, Travis I., additional, Getz, Gad, additional, Beroukhim, Rameen, additional, Gabriel, Stacey B., additional, Ally, Adrian, additional, Balasundaram, Miruna, additional, Birol, Inanc, additional, Brooks, Denise, additional, Butterfield, Yaron S.N., additional, Chuah, Eric, additional, Clarke, Amanda, additional, Dhalla, Noreen, additional, Guin, Ranabir, additional, Holt, Robert A., additional, Kasaian, Katayoon, additional, Lee, Darlene, additional, Li, Haiyan I., additional, Lim, Emilia, additional, Ma, Yussanne, additional, Mayo, Michael, additional, Moore, Richard A., additional, Mungall, Andrew J., additional, Schein, Jacqueline E., additional, Sipahimalani, Payal, additional, Tam, Angela, additional, Thiessen, Nina, additional, Wong, Tina, additional, Jones, Steven J.M., additional, Marra, Marco A., additional, Auman, J. Todd, additional, Tan, Donghui, additional, Meng, Shaowu, additional, Jones, Corbin D., additional, Hoadley, Katherine A., additional, Mieczkowski, Piotr A., additional, Mose, Lisle E., additional, Jefferys, Stuart R., additional, Roach, Jeffrey, additional, Veluvolu, Umadevi, additional, Wilkerson, Matthew D., additional, Waring, Scot, additional, Buda, Elizabeth, additional, Wu, Junyuan, additional, Bodenheimer, Tom, additional, Hoyle, Alan P., additional, Simons, Janae V., additional, Soloway, Mathew G., additional, Balu, Saianand, additional, Parker, Joel S., additional, Hayes, D. Neil, additional, Perou, Charles M., additional, Weisenberger, Daniel J., additional, Bootwalla, Moiz S., additional, Triche, Timothy, additional, Lai, Phillip H., additional, Van Den Berg, David J., additional, Baylin, Stephen B., additional, Chen, Fengju, additional, Coarfa, Cristian, additional, Noble, Michael S., additional, DiCara, Daniel, additional, Zhang, Hailei, additional, Cho, Juok, additional, Heiman, David I., additional, Gehlenborg, Nils, additional, Voet, Doug, additional, Lin, Pei, additional, Frazer, Scott, additional, Stojanov, Petar, additional, Liu, Yingchun, additional, Zou, Lihua, additional, Kim, Jaegil, additional, Lawrence, Michael S., additional, Protopopov, Alexei, additional, Song, Xingzhi, additional, Zhang, Jianhua, additional, Pantazi, Angeliki, additional, Hadjipanayis, Angela, additional, Lee, Eunjung, additional, Luquette, Lovelace J., additional, Lee, Semin, additional, Parfenov, Michael, additional, Santoso, Netty, additional, Seidman, Jonathan, additional, Xu, Andrew W., additional, Park, Peter J., additional, Lee, Junehawk, additional, Roberts, Steven A., additional, Klimczak, Leszek J., additional, Fargo, David, additional, Lang, Martin, additional, Choi, Yoon-La, additional, Lee, June-Koo, additional, Wang, Wenyi, additional, Fan, Yu, additional, Ahn, Jaeil, additional, Akbani, Rehan, additional, Weinstein, John N., additional, Haussler, David, additional, Ma, Singer, additional, Radenbaugh, Amie, additional, Zhul, Jingchun, additional, Lichtenberg, Tara M., additional, Zmuda, Erik, additional, Black, Aaron D., additional, Hanf, Benjamin, additional, Ramirez, Nilsa C., additional, Wise, Lisa, additional, Bowen, Jay, additional, Leraas, Kristen M., additional, Hall, Tracy M., additional, Gastier-Foster, Julie M., additional, Kaelin, William G., additional, Thorne, Leigh, additional, Boice, Lori, additional, Huang, Mei, additional, Vocke, Cathy, additional, Peterson, James, additional, Worrell, Robert, additional, Merino, Maria, additional, Czerniak, Bogdan A., additional, Aldape, Kenneth D., additional, Wood, Christopher G., additional, Spellman, Paul T., additional, Atkins, Michael B., additional, Cheville, John, additional, Thompson, R. Houston, additional, Jensen, Mark A., additional, Pihl, Todd, additional, Wan, Yunhu, additional, Ayala, Brenda, additional, Baboud, Julien, additional, Velaga, Sudhakar, additional, Walton, Jessica, additional, Liu, Jia, additional, Chudamani, Sudha, additional, Wu, Ye, additional, Sheth, Margi, additional, Mills Shaw, Kenna R., additional, Demchok, John A., additional, Davidsen, Tanja, additional, Yang, Liming, additional, Wang, Zhining, additional, Tarnuzzer, Roy W., additional, Zhang, Jiashan, additional, Eley, Greg, additional, Felau, Ina, additional, Zenklusen, Jean Claude, additional, Hutter, Carolyn M., additional, Guyer, Mark S., additional, Ozenberger, Bradley A., additional, and Sofia, Heidi J., additional

Published
2014
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61. Integrated genomic characterization of oesophageal carcinoma

Author

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

Subjects
3. Good health
Abstract

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.

62. Resource requirements to accelerate clinical applications of next-generation sequencing and radiomics: workshop commentary and review.

Author

Harris L, Shankar LK, Hildebrandt C, Rubinstein WS, Langlais K, Rodriguez H, Berger A, Freymann J, Huang EP, Williams PM, Zenklusen JC, Ochs R, Tezak Z, and Sahiner B

Subjects
Humans, United States, Artificial Intelligence, Machine Learning, United States Food and Drug Administration, Neoplasms genetics, Neoplasms diagnostic imaging, National Institutes of Health (U.S.), Radiomics, High-Throughput Nucleotide Sequencing methods
Abstract

The National Institutes of Health-US Food and Drug Administration Joint Leadership Council Next-Generation Sequencing and Radiomics Working Group was formed by the National Institutes of Health-Food and Drug Administration Joint Leadership Council to promote the development and validation of innovative next-generation sequencing tests, radiomic tools, and associated data analysis and interpretation enhanced by artificial intelligence and machine learning technologies. A 2-day workshop was held on September 29-30, 2021, to convene members of the scientific community to discuss how to overcome the "ground truth" gap that has frequently been acknowledged as 1 of the limiting factors impeding high-quality research, development, validation, and regulatory science in these fields. This report provides a summary of the resource gaps identified by the working group and attendees, highlights existing resources and the ways they can potentially be employed to accelerate growth in these fields, and presents opportunities to support next-generation sequencing and radiomic tool development and validation using technologies such as artificial intelligence and machine learning., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2024
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63. The Childhood Cancer Data Initiative: Using the Power of Data to Learn From and Improve Outcomes for Every Child and Young Adult With Pediatric Cancer.

Author

Flores-Toro JA, Jagu S, Armstrong GT, Arons DF, Aune GJ, Chanock SJ, Hawkins DS, Heath A, Helman LJ, Janeway KA, Levine JE, Miller E, Penberthy L, Roberts CWM, Shalley ER, Shern JF, Smith MA, Staudt LM, Volchenboum SL, Zhang J, Zenklusen JC, Lowy DR, Sharpless NE, Guidry Auvil JM, Kerlavage AR, Widemann BC, Reaman GH, Kibbe WA, and Doroshow JH

Subjects
Adolescent, United States epidemiology, Humans, Child, Young Adult, Ecosystem, Data Collection, National Cancer Institute (U.S.), Neoplasms therapy
Abstract

Data-driven basic, translational, and clinical research has resulted in improved outcomes for children, adolescents, and young adults (AYAs) with pediatric cancers. However, challenges in sharing data between institutions, particularly in research, prevent addressing substantial unmet needs in children and AYA patients diagnosed with certain pediatric cancers. Systematically collecting and sharing data from every child and AYA can enable greater understanding of pediatric cancers, improve survivorship, and accelerate development of new and more effective therapies. To accomplish this goal, the Childhood Cancer Data Initiative (CCDI) was launched in 2019 at the National Cancer Institute. CCDI is a collaborative community endeavor supported by a 10-year, $50-million (in US dollars) annual federal investment. CCDI aims to learn from every patient diagnosed with a pediatric cancer by designing and building a data ecosystem that facilitates data collection, sharing, and analysis for researchers, clinicians, and patients across the cancer community. For example, CCDI's Molecular Characterization Initiative provides comprehensive clinical molecular characterization for children and AYAs with newly diagnosed cancers. Through these efforts, the CCDI strives to provide clinical benefit to patients and improvements in diagnosis and care through data-focused research support and to build expandable, sustainable data resources and workflows to advance research well past the planned 10 years of the initiative. Importantly, if CCDI demonstrates the success of this model for pediatric cancers, similar approaches can be applied to adults, transforming both clinical research and treatment to improve outcomes for all patients with cancer.

Published
2023
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64. The Exceptional Responders Initiative: Feasibility of a National Cancer Institute Pilot Study.

Author

Conley BA, Staudt L, Takebe N, Wheeler DA, Wang L, Cardenas MF, Korchina V, Zenklusen JC, McShane LM, Tricoli JV, Williams PM, Lubensky I, O'Sullivan-Coyne G, Kohn E, Little RF, White J, Malik S, Harris LN, Mann B, Weil C, Tarnuzzer R, Karlovich C, Rodgers B, Shankar L, Jacobs PM, Nolan T, Berryman SM, Gastier-Foster J, Bowen J, Leraas K, Shen H, Laird PW, Esteller M, Miller V, Johnson A, Edmondson EF, Giordano TJ, Kim B, and Ivy SP

Subjects
Adult, Aged, Aged, 80 and over, Feasibility Studies, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Mutation genetics, National Cancer Institute (U.S.), Neoplasms epidemiology, Neoplasms pathology, Pilot Projects, Precision Medicine, Retrospective Studies, Sequence Analysis, RNA, United States epidemiology, Exome Sequencing, Neoplasms drug therapy, Neoplasms genetics, Transcriptome genetics
Abstract

Background: Tumor molecular profiling from patients experiencing exceptional responses to systemic therapy may provide insights into cancer biology and improve treatment tailoring. This pilot study evaluates the feasibility of identifying exceptional responders retrospectively, obtaining pre-exceptional response treatment tumor tissues, and analyzing them with state-of-the-art molecular analysis tools to identify potential molecular explanations for responses., Methods: Exceptional response was defined as partial (PR) or complete (CR) response to a systemic treatment with population PR or CR rate less than 10% or an unusually long response (eg, duration >3 times published median). Cases proposed by patients' clinicians were reviewed by clinical and translational experts. Tumor and normal tissue (if possible) were profiled with whole exome sequencing and, if possible, targeted deep sequencing, RNA sequencing, methylation arrays, and immunohistochemistry. Potential germline mutations were tracked for relevance to disease., Results: Cases reflected a variety of tumors and standard and investigational treatments. Of 520 cases, 476 (91.5%) were accepted for further review, and 222 of 476 (46.6%) proposed cases met requirements as exceptional responders. Clinical data were obtained from 168 of 222 cases (75.7%). Tumor was provided from 130 of 168 cases (77.4%). Of 117 of the 130 (90.0%) cases with sufficient nucleic acids, 109 (93.2%) were successfully analyzed; 6 patients had potentially actionable germline mutations., Conclusion: Exceptional responses occur with standard and investigational treatment. Retrospective identification of exceptional responders, accessioning, and sequencing of pretreatment archived tissue is feasible. Data from molecular analyses of tumors, particularly when combining results from patients who received similar treatments, may elucidate molecular bases for exceptional responses., (Published by Oxford University Press 2020. This work is written by US Government employees and is in the public domain in the US.)

Published
2021
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65. A Practical Guide to The Cancer Genome Atlas (TCGA).

Author

Wang Z, Jensen MA, and Zenklusen JC

Subjects
Animals, Humans, Neoplasms metabolism, Software, Web Browser, Computational Biology methods, Databases, Genetic, Genomics methods, Neoplasms genetics
Abstract

The Cancer Genome Atlas (TCGA) is one of the most ambitious and successful cancer genomics programs to date. The TCGA program has generated, analyzed, and made available genomic sequence, expression, methylation, and copy number variation data on over 11,000 individuals who represent over 30 different types of cancer. This chapter provides a brief overview of the TCGA program and detailed instructions and tips for investigators on how to find, access, and download this data.

Published
2016
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66. Towards patient-based cancer therapeutics.

Author

Schreiber SL, Shamji AF, Clemons PA, Hon C, Koehler AN, Munoz B, Palmer M, Stern AM, Wagner BK, Powers S, Lowe SW, Guo X, Krasnitz A, Sawey ET, Sordella R, Stein L, Trotman LC, Califano A, Dalla-Favera R, Ferrando A, Iavarone A, Pasqualucci L, Silva J, Stockwell BR, Hahn WC, Chin L, DePinho RA, Boehm JS, Gopal S, Huang A, Root DE, Weir BA, Gerhard DS, Zenklusen JC, Roth MG, White MA, Minna JD, MacMillan JB, and Posner BA

Subjects
Animals, Disease Models, Animal, Drug Discovery, Gene Regulatory Networks genetics, Humans, Mice, National Cancer Institute (U.S.), Neoplasm Proteins metabolism, Neoplasms genetics, RNA, Small Interfering metabolism, United States, Antineoplastic Agents therapeutic use, Neoplasms drug therapy, Precision Medicine
Published
2010
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67. Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC, nuclear factor-kappaB, and glucose regulation.

Author

Kotliarova S, Pastorino S, Kovell LC, Kotliarov Y, Song H, Zhang W, Bailey R, Maric D, Zenklusen JC, Lee J, and Fine HA

Subjects
Animals, Blotting, Western, Caspases metabolism, Cell Nucleus metabolism, Cell Proliferation, Enzyme-Linked Immunosorbent Assay, Glioblastoma metabolism, Glycogen Synthase Kinase 3 genetics, Glycogen Synthase Kinase 3 metabolism, Humans, Immunoenzyme Techniques, Mice, Mice, Nude, Mice, SCID, Mitochondria metabolism, Phosphorylation, RNA, Small Interfering pharmacology, Signal Transduction, TNF-Related Apoptosis-Inducing Ligand metabolism, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Apoptosis, Glioblastoma pathology, Glucose metabolism, Glycogen Synthase Kinase 3 antagonists & inhibitors, NF-kappa B metabolism, Proto-Oncogene Proteins c-myc metabolism
Abstract

Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, is involved in diverse cellular processes ranging from nutrient and energy homeostasis to proliferation and apoptosis. Its role in glioblastoma multiforme has yet to be elucidated. We identified GSK3 as a regulator of glioblastoma multiforme cell survival using microarray analysis and small-molecule and genetic inhibitors of GSK3 activity. Various molecular and genetic approaches were then used to dissect out the molecular mechanisms responsible for GSK3 inhibition-induced cytotoxicity. We show that multiple small molecular inhibitors of GSK3 activity and genetic down-regulation of GSK3alpha/beta significantly inhibit glioma cell survival and clonogenicity. The potency of the cytotoxic effects is directly correlated with decreased enzyme activity-activating phosphorylation of GSK3alpha/beta Y276/Y216 and with increased enzyme activity inhibitory phosphorylation of GSK3alpha S21. Inhibition of GSK3 activity results in c-MYC activation, leading to the induction of Bax, Bim, DR4/DR5, and tumor necrosis factor-related apoptosis-inducing ligand expression and subsequent cytotoxicity. Additionally, down-regulation of GSK3 activity results in alteration of intracellular glucose metabolism resulting in dissociation of hexokinase II from the outer mitochondrial membrane with subsequent mitochondrial destabilization. Finally, inhibition of GSK3 activity causes a dramatic decrease in intracellular nuclear factor-kappaB activity. Inhibition of GSK3 activity results in c-MYC-dependent glioma cell death through multiple mechanisms, all of which converge on the apoptotic pathways. GSK3 may therefore be an important therapeutic target for gliomas. Future studies will further define the optimal combinations of GSK3 inhibitors and cytotoxic agents for use in gliomas and other cancers.

Published
2008
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