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17 results on '"Daniel DiCara"'

1. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas

Author: Noreen Dhalla, Saianand Balu, Alexander Potapov, Yiling Lu, Antonio Iavarone, Roel G.W. Verhaak, Alessandro Perin, Bradley A. Murray, Lee Lichtenstein, Nils Gehlenborg, Zhenlin Ju, Simon G. Coetzee, Stephanie Weaver, Gaetano Finocchiaro, Susan M. Staugaitis, Scott Morris, Da Yang, Rosy Singh, Erik Zmuda, Wei Zhang, Aaron D. Black, Roger E. McLendon, J. Bradley Elder, J. Todd Auman, Arvind Rao, Harshad S. Mahadeshwar, Yunhu Wan, Liming Yang, Stacey Gabriel, Andreas Unterberg, Adam E. Flanders, Piotr A. Mieczkowski, Jianjiong Gao, Robert Penny, Andrew Wei Xu, Peter W. Laird, Gad Getz, Cynthia Taylor, Adrian Ally, Ilya Shmulevich, Tina Wong, Christopher M. McPherson, Heidi J. Sofia, Matthew G. Soloway, Jonna Grimsby, Caterina Giannini, Mark L. Cohen, Johanna Gardner, Semin Lee, Alan P. Hoyle, Jianhua Zhang, Thais S. Sabedot, Felicia Williams, Mia Grifford, Daniela Pretti da Cunha Tirapelli, David Van Den Berg, Margi Sheth, Ye Wu, Jenny Eschbacher, Marco A. Marra, Katherine A. Hoadley, Angeliki Pantazi, Chris Benz, Michael S. Noble, Christopher R. Pierson, Kristen M. Leraas, Roy Tarnuzzer, Suzanne Sifri, Huandong Sun, Greg Eley, Eyas M. Hattab, David I. Heiman, Rehan Akbani, Todd Pihl, Michael Parfenov, Erwin G. Van Meir, Jill S. Barnholtz-Sloan, Peggy Yena, Josh Stuart, Richard A. Moore, Toshinori Hinoue, Kelly Senecal, Andrew D. Cherniack, Donald W. Parsons, Rileen Sinha, Dennis T. Maglinte, Timothy A. Chan, Reanne Bowlby, Phuong L. Nguyen, Juok Cho, Andrew E. Sloan, Alexei Protopopov, Matthew Schniederjan, Yun Wang, Yuexin Liu, Rameen Beroukhim, Kristian Cibulskis, Ty Abel, Ronald E. Warnick, Sahil Seth, Richard A. Gibbs, Rebecca Duell, W. Kimryn Rathmell, Jay Bowen, Michael S. Lawrence, Darell D. Bigner, Mary McGraw, Wen-Bin Liu, Xiaojia Ren, Umadevi Veluvolu, Erin Curley, Lynda Chin, Andy Chu, Laila M. Poisson, Harindra Arachchi, Jean C. Zenklusen, Ardene Noss, Sue E. Bell, Karen Devine, Moiz S. Bootwalla, Rebecca Carlsen, David Mallery, Eric S. Lipp, Hailei Zhang, Bradley A. Ozenberger, Andrew J. Mungall, Amie Radenbaugh, Luciano Neder, Sol Katzman, Lisa Iype, Shaowu Meng, Wendi Barrett, S. Onur Sumer, Katie Dicostanzo, Mark Vitucci, Phillip H. Lai, Vsevolod Shurkhay, D. Neil Hayes, Jiabin Tang, Hui Shen, Christopher A. Bristow, Stefania Cuzzubbo, Quinn T. Ostrom, Yasin Senbabaoglu, Ruth Steele, Peter J. Park, Jacqueline E. Schein, Lior Pachter, Jia Liu, Payal Sipahimalani, Angela Hadjipanayis, Scott L. Carter, Donghui Tan, Travis I. Zack, Kristen Shimmel, Steven E. Schumacher, Leigh B. Thorne, Kenna R. Mills Shaw, Troy Shelton, Julien Baboud, Jianan Zhang, Olga Potapova, Stuart R. Jefferys, Andreas von Deimling, B. Arman Aksoy, Carrie Sougnez, Howard Colman, Tom Mikkelsen, Amanda Clarke, Houtan Noushmehr, Daniel Crain, Mark A. Jensen, D L Rotin, Stephen B. Baylin, Barry S. Taylor, Gordon Saksena, Benito Campos, Sudha Chudamani, Ouida Liu, Lisle E. Mose, Jonathan G. Seidman, Corbin D. Jones, Norman L. Lehman, Eric S. Lander, David Haussler, Franklin W. Huang, Nina Thiessen, Charles M. Perou, Gregory N. Fuller, Kosuke Yoshihara, C. Ryan Miller, Brenda Ayala, Dina Aziz, Sara Sadeghi, Cameron Brennan, Randy Mandt, Aditya Raghunathan, Jeffrey Roach, Robert A. Holt, Timothy J. Triche, Barbara Tabak, Kenneth Aldape, John N. Weinstein, Kevin Lau, Ady Kendler, Lee Cooper, Carlos Gilberto Carlotti, Siyuan Zheng, Isaac Joseph, Jason T. Huse, Steven J.M. Jones, Brady Bernard, Chip Stewart, Lixing Yang, Lisa Wise, A. Gordon Robertson, Ronglai Shen, Lisa Scarpace, Richard Kreisberg, Shiyun Ling, Michael Mayo, Jordonna Fulop, Cathy Brewer, Denise Brooks, Daniel E. Carlin, Nils Weinhold, Angela Tam, Beth Hermes, Kalle Leinonen, Giovanni Ciriello, Mahitha Vallurupalli, John A. Demchok, Bianca Pollo, Christel Herold-Mende, Rajan Jain, Liu Xi, Francesco DiMeco, Nilsa C. Ramirez, Tara M. Lichtenberg, Ashley Fehrenbach, Yingchun Liu, Miruna Balasundaram, Sofie R. Salama, Rivka R. Colen, Olena Morozova, Yussanne Ma, Zhining Wang, W. K. Alfred Yung, Scott R. VandenBerg, Esther Rheinbay, Junyuan Wu, Katayoon Kasaian, Tanja M. Davidsen, William A. Friedman, Kathy Smolenski, Yichao Sun, Anders Jacobsen, Chiara Calatozzolo, Matthew D. Wilkerson, Lucia Cuppini, Gordon B. Mills, Xingzhi Song, Joseph Paulauskis, Jaegil Kim, Pei Lin, Scott Frazer, William M. Lee, Evan O. Paull, Sheila A. Fisher, Carolyn M. Hutter, Janae V. Simons, Gene Barnett, Mara Rosenberg, Scot Waring, Timothy R. Fennell, Raju Kucherlapati, Christine Jungk, Martin L. Ferguson, Julie M. Gastier-Foster, Cathy Schilero, Yingli Wolinsky, Rohini Raman, Zack Sanborn, Ranabir Guin, Matthew Meyerson, Daniel J. Brat, Cheryl A. Palmer, Nikolaus Schultz, Erik P. Sulman, Eric Chuah, Mark E. Sherman, Theo A. Knijnenburg, Mitchel S. Berger, Lihua Zou, Hoon Kim, Daniel DiCara, Sam Ng, Joel S. Parker, Sheila Reynolds, Raffaele Nunziata, Daniel J. Weisenberger, Natalie Tasman, Chris Sander, Doug Voet, Yaron S.N. Butterfield, Brian P. O'Neill, Lori Boice, Brat D.J., Verhaak R.G.W., Aldape K.D., Yung W.K.A., Salama S.R., Cooper L.A.D., Rheinbay E., Miller C.R., Vitucci M., Morozova O., Robertson A.G., Noushmehr H., Laird P.W., Cherniack A.D., Akbani R., Huse J.T., Ciriello G., Poisson L.M., Barnholtz-Sloan J.S., Berger M.S., Brennan C., Colen R.R., Colman H., Flanders A.E., Giannini C., Grifford M., Iavarone A., Jain R., Joseph I., Kim J., Kasaian K., Mikkelsen T., Murray B.A., O'Neill B.P., Pachter L., Parsons D.W., Sougnez C., Sulman E.P., Vandenberg S.R., Van Meir E.G., Von Deimling A., Zhang H., Crain D., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton T., Sherman M., Yena P., Black A., Bowen J., Dicostanzo K., Gastier-Foster J., Leraas K.M., Lichtenberg T.M., Pierson C.R., Ramirez N.C., Taylor C., Weaver S., Wise L., Zmuda E., Davidsen T., Demchok J.A., Eley G., Ferguson M.L., Hutter C.M., Shaw K.R.M., Ozenberger B.A., Sheth M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Ayala B., Baboud J., Chudamani S., Jensen M.A., Liu J., Pihl T., Raman R., Wan Y., Wu Y., Ally A., Auman J.T., Balasundaram M., Balu S., Baylin S.B., Beroukhim R., Bootwalla M.S., Bowlby R., Bristow C.A., Brooks D., Butterfield Y., Carlsen R., Carter S., Chin L., Chu A., Chuah E., Cibulskis K., Clarke A., Coetzee S.G., Dhalla N., Fennell T., Fisher S., Gabriel S., Getz G., Gibbs R., Guin R., Hadjipanayis A., Hayes D.N., Hinoue T., Hoadley K., Holt R.A., Hoyle A.P., Jefferys S.R., Jones S., Jones C.D., Kucherlapati R., Lai P.H., Lander E., Lee S., Lichtenstein L., Ma Y., Maglinte D.T., Mahadeshwar H.S., Marra M.A., Mayo M., Meng S., Meyerson M.L., Mieczkowski P.A., Moore R.A., Mose L.E., Mungall A.J., Pantazi A., Parfenov M., Park P.J., Parker J.S., Perou C.M., Protopopov A., Ren X., Roach J., Sabedot T.S., Schein J., Schumacher S.E., Seidman J.G., Seth S., Shen H., Simons J.V., Sipahimalani P., Soloway M.G., Song X., Sun H., Tabak B., Tam A., Tan D., Tang J., Thiessen N., Triche T., Van Den Berg D.J., Veluvolu U., Waring S., Weisenberger D.J., Wilkerson M.D., Wong T., Wu J., Xi L., Xu A.W., Zack T.I., Zhang J., Aksoy B.A., Arachchi H., Benz C., Bernard B., Carlin D., Cho J., DiCara D., Frazer S., Fuller G.N., Gao J., Gehlenborg N., Haussler D., Heiman D.I., Iype L., Jacobsen A., Ju Z., Katzman S., Kim H., Knijnenburg T., Kreisberg R.B., Lawrence M.S., Lee W., Leinonen K., Lin P., Ling S., Liu W., Liu Y., Lu Y., Mills G., Ng S., Noble M.S., Paull E., Rao A., Reynolds S., Saksena G., Sanborn Z., Sander C., Schultz N., Senbabaoglu Y., Shen R., Shmulevich I., Sinha R., Stuart J., Sumer S.O., Sun Y., Tasman N., Taylor B.S., Voet D., Weinhold N., Weinstein J.N., Yang D., Yoshihara K., Zheng S., Zhang W., Zou L., Abel T., Sadeghi S., Cohen M.L., Eschbacher J., Hattab E.M., Raghunathan A., Schniederjan M.J., Aziz D., Barnett G., Barrett W., Bigner D.D., Boice L., Brewer C., Calatozzolo C., Campos B., Carlotti C.G., Chan T.A., Cuppini L., Curley E., Cuzzubbo S., Devine K., DiMeco F., Duell R., Elder J.B., Fehrenbach A., Finocchiaro G., Friedman W., Fulop J., Gardner J., Hermes B., Herold-Mende C., Jungk C., Kendler A., Lehman N.L., Lipp E., Liu O., Mandt R., McGraw M., Mclendon R., McPherson C., Neder L., Nguyen P., Noss A., Nunziata R., Ostrom Q.T., Palmer C., Perin A., Pollo B., Potapov A., Potapova O., Rathmell W.K., Rotin D., Scarpace L., Schilero C., Senecal K., Shimmel K., Shurkhay V., Sifri S., Singh R., Sloan A.E., Smolenski K., Staugaitis S.M., Steele R., Thorne L., Tirapelli D.P.C., Unterberg A., Vallurupalli M., Wang Y., Warnick R., Williams F., Wolinsky Y., Bell S., Rosenberg M., Stewart C., Huang F., Grimsby J.L., and Radenbaugh A.J.
Subjects: Adult, Male, Pathology, medicine.medical_specialty, IDH1, Adolescent, Kaplan-Meier Estimate, 1p/19q Codeletion, Biology, Article, Glioma, Molecular genetics, Grade II Glioma, medicine, Cluster Analysis, Humans, neoplasms, Exome, ATRX, Proportional Hazards Models, Aged, Cluster Analysi, DNA, Neoplasm, Sequence Analysis, DNA, General Medicine, Middle Aged, Genes, p53, medicine.disease, Chromosomes, Human, Pair 1, Mutation, Proportional Hazards Model, Cancer research, GLIOMA, Female, Oligodendroglioma, Neoplasm Grading, Glioblastoma, Chromosomes, Human, Pair 19, Human, Signal Transduction
Abstract: BACKGROUND: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. METHODS: We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. RESULTS: Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. CONCLUSIONS: The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.)
Published: 2015
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2. Comprehensive genomic characterization of head and neck squamous cell carcinomas

Author: Ni Zhao, Carter Van Waes, Lori Boice, Ashley H. Salazar, Petar Stojanov, Michael B. Prystowsky, Akinyemi I. Ojesina, Tara M. Lichtenberg, Nikolaus Schultz, Joshua M. Stuart, Mitchell J. Frederick, Julie M. Gastier-Foster, Jeffrey N. Myers, Bradley A. Ozenberger, Margaret L. Gulley, Jean C. Zenklusen, Inanc Birol, Christina Yau, Mark E. Sherman, Saianand Balu, Angela Hadjipanayis, Barry S. Taylor, Piotr A. Mieczkowski, Anthony Saleh, Carol G. Shores, Ezra E.W. Cohen, Joonil Jung, Ari B. Kahn, Lisa Wise, Peter S. Hammerman, Pei Lin, Marc Ladanyi, Mark C. Weissler, Scott L. Carter, Michele C. Hayward, Rehan Akbani, Todd Pihl, J. Jack Lee, Sophie C. Egea, Harshad S. Mahadeshwar, Leigh B. Thorne, Matthew G. Soloway, Troy Shelton, Andrea Haddad, William N. William, Wiktoria Maria Suchorska, Johanna Gardner, Marco A. Marra, Julie Ahn, Travis I. Zack, Lihua Zou, Bayardo Perez-Ordonez, David A. Wheeler, Daniel Crain, Adrian Ally, Deepak Srinivasan, Jay Bowen, Aaron D. Black, Jing Wang, Ludmila Danilova, Roy Tarnuzzer, Brenda Diergaarde, Tod D. Casasent, Dean Cheng, Giovanni Ciriello, Ken Burnett, Jeff Bruce, Wojciech Golusiński, Jonathan G. Seidman, Corbin D. Jones, Daniel J. Weisenberger, Lisa A. Peterson, Thomas M. Harris, Angeliki Pantazi, Nina Thiessen, Curtis R. Pickering, Chandra Sekhar Pedamallu, Yingchun Liu, William Lee, Andrzej Mackiewicz, Hailei Zhang, Ronglai Shen, B. Arman Aksoy, Lixing Yang, Jeffrey Roach, Simion I. Chiosea, John Waldron, David Van Den Berg, James Stephen Marron, Tanja Davidsen, Liming Yang, Maciej Wiznerowicz, Benjamin Gross, Paul M. Weinberger, Yufeng Liu, Reanne Bowlby, Zhixiang Zuo, Bartosz Szybiak, Roni J. Bollag, Samuel S. Freeman, Heather M. Walline, Gad Getz, Scott Morris, Michael S. Noble, Charles Saller, Sahil Seth, Richard A. Gibbs, Jonathan C. Irish, Hollie A. Harper, George E. Sandusky, S. Onur Sumer, Trevor Hackman, Gordon B. Mills, Carol R. Bradford, Payal Sipahimalani, Nipun Kakkar, Robert Penny, Jennifer Drummond, Adam M. Zanation, Rebecca Carlsen, Andrew J. Mungall, Harshavardhan Doddapaneni, James G. Herman, Sylvia Wrenn, Andy Chu, Nilsa C. Ramirez, Patrick Kwok Shing Ng, Patrick K. Kimes, Tina Wong, Mark E. Prince, Han Si, Kristian Cibulskis, Katherine Tarvin, Peter W. Laird, Jiabin Tang, Raja R. Seethala, Michael Parfenov, Jan F. Prins, Erin Curley, Hui Cheng, Donna M. Muzny, Lynda Chin, D. Neil Hayes, Margi Sheth, Carmen Gomez-Fernandez, Jessica Walton, Paul C. Boutros, Ariane Nguyen, Kristen M. Leraas, Robert L. Ferris, Greg Eley, Christopher C. Benz, Jaegil Kim, Thomas E. Carey, Douglas B. Chepeha, Janae V. Simons, Jiexin Zhang, Laura S. Rozek, Maureen A. Sartor, Christopher A. Bristow, Justin A. Bishop, Adel K. El-Naggar, Nishant Agrawal, Yiling Lu, Carrie Sougnez, Evan G. Taylor, Raju Kucherlapati, Scott M. Lippman, Colleen Mitchell, Wendell G. Yarbrough, Chu Chen, Donghui Tan, Bhishamjit S. Chera, Michael Mayo, Wenbin Liu, Ranabir Guin, W. Kimryn Rathmell, Mayya Malakh, Jessica Frick, John N. Weinstein, Kevin Lau, Michelle Q. Pham, Gideon Dresdner, Luc G. T. Morris, David Mallery, Zhining Wang, Yichao Sun, Lynn M. Herbert, Christine M. Komarck, Lauren Averett Byers, Angela Tam, Thomas Bodenheimer, Doug Voet, Christie Kovar, Junyuan Wu, Walker Hale, Charles M. Perou, Angela B.Y. Hui, Kenna R. Mills Shaw, Timothy J. Triche, Dong Zeng, Steven J.M. Jones, Matthew D. Wilkerson, Jinze Liu, Yan Guo, Hsu Chao, Tamara R. Jones, Katherine A. Hoadley, Stuart R. Jefferys, Thomas C. Motter, Matthew Meyerson, Konstanty Korski, Timothy A. Chan, Mark A. Jensen, Julien Baboud, Alexei Protopopov, David I. Heiman, Nils Gehlenborg, Heidi J. Sofia, Aaron D. Tward, Eric S. Lander, Yunhu Wan, Scot Waring, Peggy Yena, Robert I. Haddad, Daniel DiCara, Gordon Saksena, Juok Cho, Richard A. Moore, Darshan Singh, Peter J. Park, Matthew Ibbs, Robert A. Holt, Andrew D. Cherniack, Tanguy Y. Seiwert, Lee Lichtenstein, Anders Jacobsen, Rameen Beroukhim, Brandee T. Brown, Stephen C. Benz, Paweł Golusiński, Vonn Walter, Lixia Diao, Erik Zmuda, Scott Frazer, Michael S. Lawrence, Nils Weinhold, Jacqueline E. Schein, Xiaojia Ren, Denise Brooks, Elizabeth Buda, Jianjiong Gao, Jianhua Zhang, William W. Shockley, J. Todd Auman, Xingzhi Song, Jennifer R. Grandis, Jonathan B. McHugh, Stacey Gabriel, Martin L. Ferguson, Jeffrey S. Reid, Joseph Paulauskis, Umadevi Veluvolu, John A. Demchok, Moiz S. Bootwalla, Fei-Fei Liu, Alan P. Hoyle, Shaowu Meng, Mei Huang, Ann Marie Egloff, Christina Beard, Liu Xi, Ricardo Ramirez, Donna Morton, Lisle E. Mose, Leslie Cope, Marjorie Romkes, Zubair Khan, Noreen Dhalla, Candace Shelton, Boris Reva, Stephen B. Baylin, Miruna Balasundaram, Psalm Haseley, Andrew Wei Xu, Yan Shi, A. Gordon Robertson, Gregory T. Wolf, Darlene Lee, Steven E. Schumacher, Semin Lee, Rileen Sinha, Dennis T. Maglinte, Haiyan I. Li, William K. Funkhouser, Yi Han, Sam Ng, Joel S. Parker, Kai Wang, Zhong Chen, You Hong Fan, Yaron S.N. Butterfield, Jeffrey S. Moyer, Robert A. Burton, David Pot, Chris Sander, Daryl Waggott, Joseph A. Califano, Netty Santoso, and Kyle Chang
Subjects: Male, DNA Copy Number Variations, Somatic cell, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, CDKN2A, Humans, HRAS, Molecular Targeted Therapy, RNA, Neoplasm, Gene, neoplasms, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, Oncogene, Genome, Human, Squamous Cell Carcinoma of Head and Neck, Wnt signaling pathway, DNA, Neoplasm, Genomics, Oncogenes, Cell cycle, 3. Good health, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Mutation, Cancer research, Carcinoma, Squamous Cell, Female, FAT1, Signal Transduction, Transcription Factors
Abstract: The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.
Published: 2015

3. The Somatic Genomic Landscape of Glioblastoma

Author: Cameron W. Brennan, Roel G.W. Verhaak, Aaron McKenna, Benito Campos, Houtan Noushmehr, Sofie R. Salama, Siyuan Zheng, Debyani Chakravarty, J. Zachary Sanborn, Samuel H. Berman, Rameen Beroukhim, Brady Bernard, Chang-Jiun Wu, Giannicola Genovese, Ilya Shmulevich, Jill Barnholtz-Sloan, Lihua Zou, Rahulsimham Vegesna, Sachet A. Shukla, Giovanni Ciriello, W.K. Yung, Wei Zhang, Carrie Sougnez, Tom Mikkelsen, Kenneth Aldape, Darell D. Bigner, Erwin G. Van Meir, Michael Prados, Andrew Sloan, Keith L. Black, Jennifer Eschbacher, Gaetano Finocchiaro, William Friedman, David W. Andrews, Abhijit Guha, Mary Iacocca, Brian P. O’Neill, Greg Foltz, Jerome Myers, Daniel J. Weisenberger, Robert Penny, Raju Kucherlapati, Charles M. Perou, D. Neil Hayes, Richard Gibbs, Marco Marra, Gordon B. Mills, Eric Lander, Paul Spellman, Richard Wilson, Chris Sander, John Weinstein, Matthew Meyerson, Stacey Gabriel, Peter W. Laird, David Haussler, Gad Getz, Lynda Chin, Christopher Benz, Wendi Barrett, Quinn Ostrom, Yingli Wolinsky, Bikash Bose, Paul T. Boulos, Madgy Boulos, Jenn Brown, Christine Czerinski, Matthew Eppley, Thelma Kempista, Teresa Kitko, Yakov Koyfman, Brenda Rabeno, Pawan Rastogi, Michael Sugarman, Patricia Swanson, Kennedy Yalamanchii, Ilana P. Otey, Yingchun Spring Liu, Yonghong Xiao, J.Todd Auman, Peng-Chieh Chen, Angela Hadjipanayis, Eunjung Lee, Semin Lee, Peter J. Park, Jonathan Seidman, Lixing Yang, Steven Kalkanis, Laila M. Poisson, Aditya Raghunathan, Lisa Scarpace, Ryan Bressler, Andrea Eakin, Lisa Iype, Richard B. Kreisberg, Kalle Leinonen, Sheila Reynolds, Hector Rovira, Vesteinn Thorsson, Matti J. Annala, Joseph Paulauskis, Erin Curley, Martha Hatfield, David Mallery, Scott Morris, Troy Shelton, Candace Shelton, Mark Sherman, Peggy Yena, Lucia Cuppini, Francesco DiMeco, Marica Eoli, Emanuela Maderna, Bianca Pollo, Marco Saini, Saianand Balu, Katherine A. Hoadley, Ling Li, C. Ryan Miller, Yan Shi, Michael D. Topal, Junyuan Wu, Gavin Dunn, Caterina Giannini, Brian P. O'Neill, B. Arman Aksoy, Yevgeniy Antipin, Laetitia Borsu, Ethan Cerami, Jianjiong Gao, Benjamin Gross, Anders Jacobsen, Marc Ladanyi, Alex Lash, Yupu Liang, Boris Reva, Nikolaus Schultz, Ronglai Shen, Nicholas D. Socci, Agnes Viale, Martin L. Ferguson, Qing-Rong Chen, John A. Demchok, Laura A.L. Dillon, Kenna R. Mills Shaw, Margi Sheth, Roy Tarnuzzer, Zhining Wang, Liming Yang, Tanja Davidsen, Mark S. Guyer, Bradley A. Ozenberger, Heidi J. Sofia, Julie Bergsten, John Eckman, Jodi Harr, Christine Smith, Kelly Tucker, Cindy Winemiller, Leigh Anne Zach, Julia Y. Ljubimova, Greg Eley, Brenda Ayala, Mark A. Jensen, Ari Kahn, Todd D. Pihl, David A. Pot, Yunhu Wan, Nathan Hansen, Parvi Hothi, Biaoyang Lin, Nameeta Shah, Jae-geun Yoon, Ching Lau, Michael Berens, Kristin Ardlie, Scott L. Carter, Andrew D. Cherniack, Mike Noble, Juok Cho, Kristian Cibulskis, Daniel DiCara, Scott Frazer, Stacey B. Gabriel, Nils Gehlenborg, Jeff Gentry, David Heiman, Jaegil Kim, Rui Jing, Eric S. Lander, Michael Lawrence, Pei Lin, Will Mallard, Robert C. Onofrio, Gordon Saksena, Steve Schumacher, Petar Stojanov, Barbara Tabak, Doug Voet, Hailei Zhang, Nathan N. Dees, Li Ding, Lucinda L. Fulton, Robert S. Fulton, Krishna-Latha Kanchi, Elaine R. Mardis, Richard K. Wilson, Stephen B. Baylin, Larry Harshyne, Mark L. Cohen, Karen Devine, Andrew E. Sloan, Scott R. VandenBerg, Mitchel S. Berger, Daniel Carlin, Brian Craft, Kyle Ellrott, Mary Goldman, Theodore Goldstein, Mia Grifford, Singer Ma, Sam Ng, Joshua Stuart, Teresa Swatloski, Peter Waltman, Jing Zhu, Robin Foss, Barbara Frentzen, Raquel McTiernan, Anthony Yachnis, Yong Mao, Rehan Akbani, Oliver Bogler, Gregory N. Fuller, Wenbin Liu, Yuexin Liu, Yiling Lu, Gordon Mills, Alexei Protopopov, Xiaojia Ren, Youting Sun, W.K. Alfred Yung, Jianhua Zhang, Ken Chen, John N. Weinstein, Moiz S. Bootwalla, Phillip H. Lai, Timothy J. Triche, David J. Van Den Berg, David H. Gutmann, Norman L. Lehman, Erwin G. VanMeir, Daniel Brat, Jeffrey J. Olson, Gena M. Mastrogianakis, Narra S. Devi, Zhaobin Zhang, Darell Bigner, Eric Lipp, and Roger McLendon
Subjects: Male, Telomerase, Proteome, REGULAÇÃO GÊNICA, Somatic cell, Mesenchymal Glioblastoma, PDGFRA, Computational biology, Biology, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, medicine, Humans, Gene Regulatory Networks, Gene, Genetics, Glioblastoma cell, Mutation, Brain Neoplasms, Biochemistry, Genetics and Molecular Biology(all), Gene Expression Profiling, Phenotype, Gene expression profiling, DNA methylation, Cancer research, Female, Glioblastoma, Signal Transduction
Abstract: SummaryWe describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.
Published: 2013
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4. Mutational heterogeneity in cancer and the search for new cancer genes

Author: Alex H. Ramos, Elizabeth Nickerson, Daniel DiCara, Kristian Cibulskis, Austin M. Dulak, Charles W. M. Roberts, Jaume Mora, Yotam Drier, Amnon Koren, Scott L. Carter, Paz Polak, Steven A. McCarroll, Melissa Parkin, Lee Lichtenstein, Eric S. Lander, Marcin Imielinski, Douglas Voet, Jens G. Lohr, Kimberly Stegmaier, Peter S. Hammerman, Dan A. Landau, Timothy Fennell, Todd R. Golub, Wendy Winckler, Sylvan C. Baca, Elena Helman, Carrie Sougnez, Chip Stewart, Gad Getz, Petar Stojanov, Bryan Hernandez, Shamil R. Sunyaev, Steven A. Roberts, Eran Hodis, Lauren Ambrogio, Andrey Sivachenko, Michael S. Noble, Daniel Auclair, Dmitry A. Gordenin, Adam J. Bass, Nicolas Stransky, Erica Shefler, Stacey Gabriel, Ryan S. Lee, Trevor J. Pugh, Craig H. Mermel, Brian D. Crompton, Kristin G. Ardlie, Jorge Melendez-Zajgla, David I. Heiman, Aaron McKenna, Michael S. Lawrence, Alfredo Hidalgo-Miranda, Pei Lin, Gordon Saksena, Jaegil Kim, Levi A. Garraway, Maria L. Cortes, Robert C. Onofrio, Gregory V. Kryukov, Adam Kiezun, Catherine J. Wu, Matthew Meyerson, Jaclyn A. Biegel, and Lihua Zou
Subjects: Mutation rate, Lung Neoplasms, DNA Replication Timing, Gene Expression, Biology, Genome, Article, 03 medical and health sciences, Genetic Heterogeneity, 0302 clinical medicine, Mutation Rate, Neoplasms, medicine, Humans, Exome, False Positive Reactions, Neoplasms, Squamous Cell, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, Genome, Human, Genetic heterogeneity, Reproducibility of Results, Cancer, Oncogenes, medicine.disease, Human genetics, 3. Good health, Sample Size, 030220 oncology & carcinogenesis, Kataegis, Mutation, Human genome, Artifacts
Abstract: Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer. These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.
Published: 2013

5. COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

Author: Kelinda Tucker, Raju Kucherlapati, Ng Sam, John N. Weinstein, Lori Boice, Satish K. Tickoo, Saianand Balu, John C. Cheville, B. Arman Aksoy, Chip Stewart, Preethi H. Gunaratne, Martin L. Ferguson, Bogdan Czerniak, Christie Kovar, Theodore C. Goldstein, Mark E. Sherman, Juan M. Mosquera, Chris Sander, Yaron S.N. Butterfield, Leigh Anne Zach, Yiling Lu, Chandra Lebovitz, Gary Witkin, David Pot, Gordon Robertson, Richard A. Gibbs, James J. Hsieh, Benjamin P. Berman, Doug Voet, Kyle Chang, W. Marston Linehan, Margaret Morgan, Joan Pontius, Jodi Harr, Lihua Zhou, Joel S. Parker, David Van Den Berg, Michael B. Atkins, Sheila Reynolds, Petar Stojanov, Joel B. Nelson, Gordon B. Mills, Toni K. Choueiri, Weimin Xiao, Hye Jung E. Chun, Ronglai Shen, Rebecca Carlsen, Jennifer Brown, Tod D. Casasent, Sabina Signoretti, Jo Ellen Weaver, Phillip H. Lai, Dominique L. Berton, Patrick Plettner, Irina Ostrovnaya, Lisle E. Mose, Leslie Cope, Nils Gehlenborg, Heidi J. Sofia, Peter J. Park, Scott Morris, Hsin-Ta Wu, Fabio Vandin, Ranabir Guin, Daniel E. Carlin, Jacqueline E. Schein, Xi Liu, Nils Weinhold, Wandaliz Torres-Garcia, Cureline Olga Potapova, Daniel DiCara, Juok Cho, Steve Schumacher, Chris Wakefield, A. Rose Brannon, Susan M. Benton, Tom Bodenheimer, J. Todd Auman, Brenda Rabeno, Sharon M. Gorski, Eric E. Snyder, Divya Kalra, Brenda Ayala, Jiashan Zhang, Zhang Wei, Kyle Ellrott, Zhining Wang, Stacey Gabriel, Dominik Stoll, Daniel L. Rubin, W. Kimryn Rathmell, Eric Chuah, David Mallery, Tanja Davidsen, David Cogdell, Anders Jacobsen, John A. Demchok, Robert C. Onofrio, Anna Chu, Piotr A. Mieczkowski, Zhiyong Ding, Erin Curley, Johanna Gardner, Robert Worrell, Hailei Zhang, Jennifer C. Fisher, Donna M. Muzny, Rajiv Dhir, Walker Hale, Ari B. Kahn, Sheila Fisher, Giovanni Ciriello, Ken Burnett, Marco A. Marra, Wiam Bshara, Anil V. Parwani, Joshua M. Stuart, Richard Varhol, Kristin G. Ardlie, Han Yi, Lisa R. Trevino, Roy Tarnuzzer, Michael S. Noble, Erin Pleasance, Jesse Walsh, Leigh B. Thorne, Andy Chu, Peter W. Laird, Andrew J. Mungall, Rashmi N. Sanbhadti, Mark Backus, David A. Wheeler, Bradley A. Ozenberger, Jodi K. Maranchie, William Mallard, Jared R. Slobodan, Christine Czerwinski, Jireh Santibanez, Andrew J. Stout, Donghui Tan, Laura S. Schmidt, Junyuan Wu, Jianjiong Gao, Daniel J. Weisenberger, D. Neil Hayes, Scott Frazer, Alan P. Hoyle, Konstantin V. Fedosenko, Rehan Akbani, Todd Pihl, Rahul Vegesna, Lynda Chin, Shelley Alonso, Jeffrey G. Reid, Donna Morton, Cathy D. Vocke, R. Houston Thompson, Christopher C. Benz, Kenna R. Mills Shaw, Liming Yang, Carmelo Gaudioso, Nianxiang Zhang, Caleb F. Davis, Carrie Hirst, Shi Yan, Michael L. Blute, Barry S. Taylor, Mathew G. Soloway, Nina Thiessen, Paul T. Spellman, Deepak Srinivasan, Yongjun Zhao, Boris Reva, Wang Min, Stuart R. Jefferys, Benjamin J. Raphael, Nicholas J. Petrelli, Arash Shafiei, Lora Lewis, Eric Jonasch, David I. Heiman, Scot Waring, Richard A. Moore, Eric S. Lander, Evan O. Paull, Hoon Kim, Janae V. Simons, Stephen B. Baylin, Gad Getz, Stanley Girshik, Victor E. Reuter, Benjamin Gross, Ethan Cerami, Andrew D. Cherniack, Christine I. Smith, Christina Yau, Michael D. Topal, Peter Waltman, Jeff Boyd, Rameen Beroukhim, Angela Tam, Yingchun Liu, Peter A. Kigonya, Miruna Balasundaram, Maria J. Merino, David Haussler, Dinh Huyen, Elizabeth Buda, Michael S. Lawrence, Lin Pei, Charles M. Perou, Timothy J. Triche, Jessica Walton, Greg Eley, Tiffany Ting Liu, Joseph Paulauskis, Matthew Meyerson, Marc Ladanyi, Jaegil Kim, Katherine A. Hoadley, Huang Mei, Ilya Shmulevich, Robin J.N. Coope, Mary Iacocca, Natasja Wye, Adrian Ally, Mark A. Rubin, A. Ari Hakimi, Lori Huelsenbeck-Dill, Steven J.M. Jones, James Peterson, Mark A. Jensen, Barbara Tabak, Andrey Sivachenko, Julie Bergsten, John Eckman, Inanc Birol, Rohini Raman, Nipun Kakkar, Christina Liquori, Rileen Sinha, Dennis T. Maglinte, Lichtenstein Lee, Haiyan I. Li, William G. Kaelin, Anna K. Unruh, Noreen Dhalla, Candace Shelton, Roel G.W. Verhaak, Christopher J. Ricketts, Carrie Sougnez, Harsha Doddapaneni, Mark S. Guyer, Robert Penny, Michael F. Berger, Margi Sheth, Darlene Lee, Dimitra Tsavachidou, Chad J. Creighton, Prachi Kothiyal, Scott L. Carter, Michael Mayo, Zhu Jing, Kenneth Aldape, Corbin D. Jones, Moiz S. Bootwalla, Payal Sipahimalani, Martin Hirst, Sean P. Barletta, Kristian Cibulskis, Jerome Myers, Matthew C. Nicholls, Yidi J. Turman, Julien Baboud, Jeff Gentry, Carl Morrison, Gordon Saksena, Troy Shelton, Swapna Mahurkar, Robert A. Holt, Robert Sfeir, Shen Hui, Suzanne S. Fei, Christopher G. Wood, Candace Carter, S. Onur Sumer, Pheroze Tamboli, Yiming Zhu, Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Getz, Gad Asher, Voet, Douglas, Lin, Pei, Chin, Lynda, and Lander, Eric Steven
Subjects: DNA Mutational Analysis, GRB10 Adaptor Protein, AMP-Activated Protein Kinases, Epigenesis, Genetic, PBRM1, Pentose Phosphate Pathway, Phosphatidylinositol 3-Kinases, RNA, Neoplasm, BAP1, Genome, Multidisciplinary, Genomics, Chromatin, Gene Expression Regulation, Neoplastic, DNA methylation, Signal transduction, Acetyl-CoA Carboxylase, Carcinoma, Renal Cell, Chromatin Assembly and Disassembly, Citric Acid Cycle, DNA Methylation, Gene Expression Profiling, Genome, Human, Histone-Lysine N-Methyltransferase, Humans, Metabolic Networks and Pathways, MicroRNAs, Mutation, PTEN Phosphohydrolase, Proto-Oncogene Proteins c-akt, Signal Transduction, Survival Analysis, Human, Biology, Article, Genetic, SETD2, microRNA, medicine, Neoplastic, Carcinoma, Renal Cell, medicine.disease, Clear cell renal cell carcinoma, Gene Expression Regulation, Cancer research, RNA, Neoplasm, Epigenesis
Abstract: Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
Published: 2013

6. Integrated genomic characterization of endometrial carcinoma

Author: Ding Li, Esther Elishaev, Linda Dao, Juok Cho, Alexei Protopopov, Heather Schmidt, Tod D. Casasent, Bobbie S. Gostout, P.J. DiSaia, Jacqueline E. Schein, J. Todd Auman, Jay Bowen, S. Onur Sumer, Beth Y. Karlan, Gordon Saksena, Prachi Kothiyal, Robert E. Pyatt, Theodore C. Goldstein, Lisle E. Mose, Paul J. Goodfellow, Brenda Ayala, Nilsa C. Ramirez, Thomas Barr, Payal Sipahimalani, Gordon B. Mills, Rebecca Carlsen, Linda Van Le, Andy Chu, Peter W. Laird, Russell Broaddus, Helga B. Salvesen, Sam Ng, Cyriac Kandoth, Christopher Adams, Yiling Lu, Donghui Tan, Peter White, Lori Boice, Saianand Balu, Daniel DiCara, Robert A. Holt, Christopher C. Benz, Shi Yan, Joel S. Parker, Jessica Frick, Adrian Ally, Boris Winterhoff, Pamela M. Pollock, Patrick Plettner, Ethan Cerami, Angela Tam, Katherine A. Hoadley, Melissa Hart-Kothari, Robert C. Onofrio, John N. Weinstein, Sheila Reynolds, David Haussler, Kristian Cibulskis, Charles M. Perou, Timothy J. Triche, Rehan Akbani, Jeff Roach, Michael Mayo, Ranabir Guin, W. Kimryn Rathmell, Carmen Helsel, Junyuan Wu, Will Mallard, Nandita Barnabas, Todd Pihl, Ruibin Xi, Nianxiang Zhang, David Mallery, Douglas A. Levine, Aaron D. Black, David I. Heiman, Sugy Kodeeswaran, Lynda Chin, Guoyan Liu, Mark E. Borowsky, Daniel J. Weisenberger, Yuexin Liu, Hailei Zhang, Kenna R. Mills Shaw, Anna K. Unruh, Andrew Berchuck, Michael Button, Noreen Dhalla, Bryan Hernandez, Rayna K. Matsuno, David G. Mutch, Chen Wang, Teresa R. Tabler, Yaron S.N. Butterfield, Jeff Gentry, Stuart R. Jefferys, Thomas Grossman, Kelley Kneile, Fanny Dao, Scot Waring, Barbara Tabak, Eric E. Snyder, Eric S. Lander, Richard A. Moore, David J. Dooling, David Van Den Berg, Jiabin Tang, Piotr A. Mieczkowski, Victoria Blanc, Wei Zhang, Inanc Birol, Harkness Kuck, Mathew G. Soloway, Johanna Gardner, Gary Witkin, Sahil Seth, Heidi J. Sofia, B. Arman Aksoy, Nikolaus Schultz, Marco A. Marra, Andrew D. Cherniack, D L Rotin, Anders Jacobsen, Erik Zmuda, Candace Carter, Christina Yau, Stephen C. Benz, Alexander A. Green, Michael D. Topal, Jean MacKenzie, Elena Nemirovich-Danchenko, Nicholas J. Petrelli, Dana Nicholson, Eve Shinbrot, Han Liang, Rameen Beroukhim, Charlenia Berry-Green, Kristin G. Ardlie, Joan Pontius, David Pot, Ari B. Kahn, Marc T. Goodman, Yevgeniy Antipin, Christopher Szeto, Jianhua Zhang, Ilya Shmulevich, Lori Huelsenbeck-Dill, Steven J.M. Jones, Carrie Sougnez, Kristen M. Leraas, Pei Lin, Robert A. Soslow, Erin Curley, Leigh B. Thorne, Hye Jung E. Chun, Michael S. Lawrence, Michelle O'Laughlin, Moiz S. Bootwalla, Lixing Yang, Mark A. Jensen, Rajiv Dhir, David A. Wheeler, C. Blake Gilks, Jianjiong Gao, Lisa Wise, Giovanni Ciriello, Joelle Kalicki-Veizer, Shaowu Meng, Mei Huang, Elaine R. Mardis, Faina Bogomolniy, Kai Ye, Jenny Lester, Lihua Zou, Hollie A. Harper, Robert Edwards, Ronglai Shen, Xiaojia Ren, Nils Weinhold, Harshad S. Mahadeshwar, Sandra Orsulic, Tom Bodenheimer, Zhenlin Ju, Chris Wakefield, Scott Frazer, John M. S. Bartlett, Gideon Dresdner, Hui Shen, Deepak Srinivasan, Aaron Hobensack, Cynthia McAllister, Marc Ladanyi, Tanja Davidsen, Lucinda Fulton, Michael D. McLellan, Richard K. Wilson, Zeng Dong, Olga Potapova, Sean C. Dowdy, Rui Jing, Kristin K. Zorn, Robert S. Fulton, Matti Annala, Chris Sander, Michael S. Noble, Benjamin Gross, Janae V. Simons, Phillip H. Lai, Laura Monovich, Andrew J. Mungall, Peter J. Park, Fedor Moiseenko, Liming Yang, Gad Getz, John Deardurff, Matthew Meyerson, Jeremy Parfitt, A. Gordon Robertson, Bradley M. Broom, Blaise A. Clarke, Greg Eley, Jennifer O. Fisher, Andrey Sivachenko, Narciso Olvera, Carrie Hirst, Adam M. Farkas, Karuna Garg, Wendy Winckler, Eric Chuah, Stacey Gabriel, Michael E. Carney, Stephen B. Baylin, Doug Voet, Miruna Balasundaram, Christine Czerwinski, Daphne W. Bell, Richard Varhol, Alexandra Meuter, Alan P. Hoyle, Darlene Lee, Elizabeth Buda, Li Ding, Xingzhi Song, Steven E. Schumacher, Anna L. Chu, Attila Teoman, Mary Iacocca, Semin Lee, Rileen Sinha, Itai Pashtan, Haiyan I. Li, Mikhail Abramov, Mark S. Guyer, Robert Penny, Margi Sheth, Scott L. Carter, Corbin D. Jones, Michael J. Birrer, Julie M. Gastier-Foster, D. Neil Hayes, Nathan Vanhoose, Brenda Rabeno, Raju Kucherlapati, Martin L. Ferguson, Joshua M. Stuart, Steve E. Kalloger, Mark G. Cadungog, Petar Stojanov, Tara M. Lichtenberg, Bradley A. Ozenberger, Angela Hadjipanayis, Barry S. Taylor, Boris Reva, Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., and Park, Peter J.
Subjects: DNA Copy Number Variations, endocrine system diseases, ARID1A, DNA Mutational Analysis, Breast Neoplasms, Biology, medicine.disease_cause, Article, Uterine serous carcinoma, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, PTEN, Exome, Poly-ADP-Ribose Binding Proteins, neoplasms, 030304 developmental biology, Chromosome Aberrations, Ovarian Neoplasms, 0303 health sciences, Endometrial intraepithelial neoplasia, Multidisciplinary, Genome, Human, Microsatellite instability, DNA Polymerase II, Genomics, medicine.disease, Molecular biology, female genital diseases and pregnancy complications, Endometrial Neoplasms, 3. Good health, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Serous fluid, 030220 oncology & carcinogenesis, DNA methylation, Cancer research, biology.protein, Female, KRAS, Signal Transduction, Transcription Factors
Abstract: We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ~25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours., National Institutes of Health (U.S.) (Grant 5U24CA143799-04), National Institutes of Health (U.S.) (Grant 5U24CA143835-04), National Institutes of Health (U.S.) (Grant 5U24CA143840-04), National Institutes of Health (U.S.) (Grant 5U24CA143843-04), National Institutes of Health (U.S.) (Grant 5U24CA143845-04), National Institutes of Health (U.S.) (Grant 5U24CA143848-04), National Institutes of Health (U.S.) (Grant 5U24CA143858-04), National Institutes of Health (U.S.) (Grant 5U24CA143866-04), National Institutes of Health (U.S.) (Grant 5U24CA143867-04), National Institutes of Health (U.S.) (Grant 5U24CA143882-04), National Institutes of Health (U.S.) (Grant 5U24CA143883-04), National Institutes of Health (U.S.) (Grant 5U24CA144025-04), National Institutes of Health (U.S.) (Grant U54HG003067-11), National Institutes of Health (U.S.) (Grant U54HG003079-10), National Institutes of Health (U.S.) (Grant U54HG003273-10)
Published: 2013
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7. A Landscape of Driver Mutations in Melanoma

Author: Nicolas Stransky, Guo Chen, Jeffrey E. Gershenwald, Daniel Auclair, Gad Getz, Andrey Sivachenko, Michael S. Noble, Daniel DiCara, Katherine Stemke-Hale, Eran Hodis, Eric S. Lander, Robert C. Onofrio, Dirk Schadendorf, Kristin G. Ardlie, Nikhil Wagle, Gregory V. Kryukov, Liren Li, Donald L. Morton, Stefan T. Arold, Douglas Voet, Kristian Cibulskis, Alex H. Ramos, Elizabeth Nickerson, Levi A. Garraway, Lynda Chin, Michael A. Davies, Wendy Winckler, Ian R. Watson, Kelly Chong, John E. Ladbury, Matthew Meyerson, Stacey Gabriel, Stephan N. Wagner, Jean Philippe Theurillat, Dave S.B. Hoon, Marcin Imielinski, Michael S. Lawrence, Jennifer A. Wargo, Chelsea S. Place, and Gordon Saksena
Subjects: Models, Molecular, Proto-Oncogene Proteins B-raf, rac1 GTP-Binding Protein, Neuroblastoma RAS viral oncogene homolog, Ultraviolet Rays, Molecular Sequence Data, Medizin, Mutagenesis (molecular biology technique), RAC1, Genome-wide association study, Biology, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Exome, Amino Acid Sequence, Melanoma, Gene, Cells, Cultured, 030304 developmental biology, Genetics, 0303 health sciences, Mutation, Biochemistry, Genetics and Molecular Biology(all), medicine.disease, Mutagenesis, 030220 oncology & carcinogenesis, Melanocytes, Sequence Alignment, Genome-Wide Association Study
Abstract: Summary Despite recent insights into melanoma genetics, systematic surveys for driver mutations are challenged by an abundance of passenger mutations caused by carcinogenic UV light exposure. We developed a permutation-based framework to address this challenge, employing mutation data from intronic sequences to control for passenger mutational load on a per gene basis. Analysis of large-scale melanoma exome data by this approach discovered six novel melanoma genes ( PPP6C , RAC1 , SNX31 , TACC1 , STK19 , and ARID2 ), three of which— RAC1 , PPP6C , and STK19 —harbored recurrent and potentially targetable mutations. Integration with chromosomal copy number data contextualized the landscape of driver mutations, providing oncogenic insights in BRAF- and NRAS-driven melanoma as well as those without known NRAS / BRAF mutations. The landscape also clarified a mutational basis for RB and p53 pathway deregulation in this malignancy. Finally, the spectrum of driver mutations provided unequivocal genomic evidence for a direct mutagenic role of UV light in melanoma pathogenesis.
Published: 2012
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8. Genomic Classification of Cutaneous Melanoma

Author: W. Kimryn Rathmell, Lauren E. Haydu, Nils Gehlenborg, David Mallery, Lynn M. Herbert, Hailei Zhang, Darlene Lee, Payal Sipahimalani, Richard A. Scolyer, Jonathan R. Stretch, Amanda Clarke, Sudha Chudamani, Dirk Schadendorf, Jeffrey Roach, Troy Shelton, Kerwin F. Shannon, Kadir C. Akdemir, Alexander J. Lazar, Lixing Yang, D. Murawa, Jingchun Zhu, Michael Mayo, Steven E. Schumacher, Marc Ladanyi, Yiling Lu, Levi A. Garraway, Andrew J. Spillane, Giandomenico Russo, Ian R. Watson, Matthew D. Wilkerson, Mei Huang, Chang Jiun Wu, Pedamallu Chandra Sekhar, Laura Brockway-Lunardi, Wiktoria Maria Suchorska, Michael A. Davies, John M. S. Bartlett, Benjamin Gross, Mark Gerken, Georgy Manikhas, William R. Jeck, Michael Dinikin, Sam Ng, Antje Sucker, Sharon K. Huang, Donghui Tan, Semin Lee, Da Yang, Yardena Samuels, Boris C. Bastian, Katherine A. Hoadley, Kenna R. Mills Shaw, Shaowu Meng, Kunal Rai, Sheila Fisher, Tom Bodenheimer, Robyn P. M. Saw, Joel S. Parker, Victoria Fulidou, Scot Waring, Vesteinn Thorsson, Jacqueline E. Schein, Heidi J. Sofia, Jia Liu, Eric S. Lander, Martin L. Miller, Scott E. Woodman, Yunhu Wan, Olga Voronina, Brenda Ayala, Moiz S. Bootwalla, Rileen Sinha, Yonathan Lissanu Deribe, Yussanne Ma, Gabriel Sica, Matthew Ibbs, Pam Bartlett, Arkadiusz Spychała, Sheila Reynolds, Nikolaus Schultz, Jianhua Zhang, Stephen B. Baylin, Saianand Balu, Jay Bowen, Eran Hodis, Olga Potapova, Lori Boice, Julie M. Gastier-Foster, Singer Ma, Victor G. Prieto, Steven J.M. Jones, Konstantin V. Fedosenko, Rehan Akbani, Todd Pihl, Ruibin Xi, Stergios J. Moschos, Lisa Iype, Robert Penny, Vonn Walter, Peter Hersey, Umadevi Veluvolu, Jiabin Tang, Mark A. Jensen, Aaron Chevalier, Nils Weinhold, Yaron S.N. Butterfield, S. Onur Sumer, Lisle E. Mose, Leslie Cope, Angela Tam, Carmelo Gaudioso, Giovanni Ciriello, Jaegil Kim, Noreen Dhalla, Candace Shelton, Andrzej Mackiewicz, Travis I. Zack, James G. Herman, Lisa Zimmer, Chia Chin Wu, Elena Pagani, Franklin W. Huang, Tanja Davidsen, Stuart R. Jefferys, Andy Chu, Harmanjatinder S. Sekhon, Richard A. Moore, Scott L. Carter, Ludmila Danilova, Peter W. Laird, Nicholas K. Hayward, Julien Baboud, A. Gordon Robertson, Scott Morris, Honorata Tatka, Gordon Saksena, Robert A. Holt, Angela Hadjipanayis, Jakub Brzezinski, Lihua Zou, Nilsa C. Ramirez, Witold Kycler, Yasin Senbabaoglu, Xingzhi Song, Barbara Tabak, Christopher C. Benz, Michael Dubina, Wei Zhang, Sophie Egea, Fedor Moiseenko, Marcus Bosenberg, Piotr A. Mieczkowski, Michael J. Quinn, Harindra Arachchi, Andrew J. Mungall, Lynn Cherney, Suresh Ramalingam, Christopher A. Bristow, Hojabr Kakavand, Chris Sander, Peiling Tsou, Anil Korkut, Alan P. Hoyle, Arshi Arora, Kenneth K. Lee, Netty Santoso, Raymond J. Cho, Ricardo Ramirez, Melissa Saul, Haiyan I. Li, Jeremy Parfitt, Valerie Jakrot, Tiffany L. Calderone, Jessica Frick, John N. Weinstein, Brady Bernard, John M. Kirkwood, Dave S.B. Hoon, Carolyn J. Shiau, Carmen Gomez-Fernandez, Michael Krauthammer, Carrie Sougnez, George E. Sandusky, Xiaojia Ren, Charles Schwallier, Carolyn M. Hutter, Radoslaw Łaźniak, Dmitry Belyaev, Richard F. Kefford, Jeffrey M. Trent, Ouida Liu, J. Stephen Ebrom, Yoon La Choi, Maciej Wiznerowicz, Ranabir Guin, Yan Shi, Ewa Leporowska, Zhenlin Ju, Charles Saller, Hyojin Kang, Jean C. Zenklusen, Tony Gutschner, Peter White, Luigi Nezi, Oxana Paklina, Harshad S. Mahadeshwar, Wiam Bshara, Roeland Verhaak, Kenneth Y. Tsai, Ilya Shmulevich, Kristian Cibulskis, Jonathan G. Seidman, Corbin D. Jones, Ayush T. Raman, D. Neil Hayes, Nandita Barnabas, Uma Rao, Jennifer Eschbacher, Timothy R. Fennell, Jeffrey E. Lee, Matthew Meyerson, Jeffrey E. Gershenwald, Elizabeth Buda, Xiaobei Zhao, Jason Roszik, M. Teresiak, Daniel DiCara, Pei Lin, Eliezer M. Van Allen, Scott Frazer, Genevieve M. Boland, Zhining Wang, Susan Hoppough, Konstanty Korski, Michael S. Noble, B. Arman Aksoy, Reanne Bowlby, Adeboye Osunkoya, Taofeek K. Owonikoko, Madhusmita Behera, Shiyun Ling, Erin Curley, Rajiv Dhir, Andrew Wei Xu, David I. Heiman, Samirkumar B. Amin, Andrew D. Cherniack, Brenna Matejka, Rameen Beroukhim, Michael S. Lawrence, Kelsey Zhu, Wen-Bin Liu, Stacey Gabriel, Martin L. Ferguson, Samantha Sharpe, Giannicola Genovese, Jay Engel, Johanna Gardner, Junyuan Wu, Marco A. Marra, Roy Tarnuzzer, John F. Thompson, Denise Brooks, Lawrence N. Kwong, Woong-Yang Park, Daniel J. Weisenberger, J. Todd Auman, Kristen M. Leraas, Margi Sheth, Riccardo Bono, John A. Demchok, Stefania D'Atri, Candace D. Carter, Miruna Balasundaram, Natalie Bir, Matthew G. Soloway, Angeliki Pantazi, Sahil Seth, Qixia A. Deng, Junehawk Lee, Dana Nicholson, Ye Wu, Keith T. Flaherty, Peter J. Park, Amie Radenbaugh, Benjamin Hanf, Katherine Tarvin, James S. Wilmott, Giancarlo Antonini Cappellini, Pawel Murawa, Maria Synott, Jonna Grimsby, Stephen Coons, Joachim Klode, Michael Button, Alyssa Janning, Alexei Protopopov, Florian L. Muller, Donald L. Morton, Joshua M. Stuart, Ina Felau, Cindy Sander, Ruth Halaban, John P. Miller, David Haussler, Monique Albert, Charles M. Perou, Timothy J. Triche, Yichao Sun, Aaron D. Black, Adrian Ally, Sousan Mehrabi, David Van Den Berg, Graham J. Mann, Erik Zmuda, Carl Morrison, Daniel Crain, Douglas Voet, Janae V. Simons, Norman E. Sharpless, Fadlo R. Khuri, Phillip H. Lai, Liming Yang, Anders Jacobsen, Keith A. Delman, Teresa R. Tabler, Gad Getz, Tara M. Lichtenberg, William Lee, Georgina V. Long, Nina Thiessen, Ronglai Shen, Francesca Passarelli, Bradley A. Ozenberger, Gordon B. Mills, Jessica Walton, Greg Eley, Leigh B. Thorne, Merrick I. Ross, Jared Malke, Barry S. Taylor, Juok Cho, William R. Burns, Michael Parfenov, Thomas Gribbin, Yuling Wang, Raju Kucherlapati, Lynda Chin, Bradley A. Murray, Lee Lichtenstein, Jianjiong Gao, and Lisa Wise
Subjects: Skin Neoplasms, Mutant, Medizin, Biology, General Biochemistry, Genetics and Molecular Biology, Subclass, Article, Transcriptome, chemistry.chemical_compound, Databases, Genetic, medicine, Humans, Gene, Melanoma, Genetics, Biochemistry, Genetics and Molecular Biology(all), Cancer, Binimetinib, medicine.disease, National Cancer Institute (U.S.), United States, 3. Good health, chemistry, Cutaneous melanoma, Mutation, Cancer research
Abstract: Summary We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF , mutant RAS , mutant NF1 , and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.
Published: 2015

9. Characterization of HPV and host genome interactions in primary head and neck cancers

Author: J. Jack Lee, Carter Van Waes, Michael B. Prystowsky, Akinyemi I. Ojesina, Joshua M. Stuart, Mitchell J. Frederick, Angela By Hui, Saianand Balu, Scot Waring, Inanc Birol, Bayardo Perez-Ordonez, Aaron D. Black, Payal Sipahimalani, Wiktoria Maria Suchorska, Michele C. Hayward, Jeffrey Roach, Adrian Ally, Ranabir Guin, Samuel S. Freeman, J. Todd Auman, Hollie A. Harper, Mark E. Prince, David Van Den Berg, Nipun Kakkar, James G. Herman, Adam M. Zanation, Nilsa C. Ramirez, Daniel DiCara, Carol R. Bradford, Paul C. Boutros, Peter W. Laird, Evan G. Taylor, Yan Shi, Jonathan M. Irish, Kristian Cibulskis, Junyuan Wu, Darlene Lee, Katherine A. Hoadley, Jeff Bruce, Yingchun Liu, Heather M. Walline, Carol G. Shores, Raju Kucherlapati, Scott M. Lippman, Colleen Mitchell, Steven E. Schumacher, Wendell G. Yarbrough, Tanguy Y. Seiwert, Sophie C. Egea, Elena Ivanova, Troy Shelton, Jiexin Zhang, Patrick K. Kimes, Nikolaus Schultz, Noreen Dhalla, Maciej Wiznerowicz, Daniel J. Weisenberger, Martin L. Ferguson, Tamara R. Jones, Haiyan I. Li, Nishant Agrawal, Yiling Lu, Lixing Yang, Brandee T. Brown, Julie M. Gastier-Foster, Nils Weinhold, Harshad S. Mahadeshwar, Angela Tam, Lihua Zou, Tom Bodenheimer, Gordon B. Mills, W. Kimryn Rathmell, David Mallery, Semin Lee, Scott J. Morris, Lynn M. Herbert, Hailei Zhang, Thomas C. Motter, Walker Hale, Tina Wong, Yichao Sun, Heidi J. Sofia, Rileen Sinha, Dennis T. Maglinte, Robert I. Haddad, Matthew D. Wilkerson, Jinze Liu, Julien Baboud, Brenda Diergaarde, Michelle Q. Pham, Tanja M. Davidsen, Maureen A. Sartor, Robert A. Holt, Angela Hadjipanayis, Pei Lin, Anders Jacobsen, Stephen C. Benz, Dean Cheng, Matthew Meyerson, Andy Chu, Ezra E.W. Cohen, Joonil Jung, Ari B. Kahn, Scott Frazer, Leigh B. Thorne, Andrew J. Mungall, David A. Wheeler, Nina Thiessen, Jay Bowen, Hui Cheng, D. Neil Hayes, Jennifer Drummond, Patrick Kwok Shing Ng, Harshavardhan Doddapaneni, S. Onur Sumer, Katherine Tarvin, John W.F. Waldron, Nils Gehlenborg, Douglas B. Chepeha, Janae V. Simons, Robert L. Ferris, Paweł Golusiński, Christina Beard, Donna Morton, Boris Reva, Psalm Haseley, Andrew Wei Xu, Giovanni Ciriello, Gregory T. Wolf, Ken Burnett, Lisa A. Peterson, Sylvia Wrenn, Mark A. Jensen, Travis I. Zack, Deepak Srinivasan, Thomas E. Carey, Lisle E. Mose, Mark E. Sherman, Leslie Cope, Adel K. El-Naggar, Marjorie Romkes, D Wheeler, Christopher A. Bristow, Andrea Haddad, Mayya Malakh, Ludmila Danilova, Jean C. Zenklusen, Jiabin Tang, Laura S. Rozek, Jon G. Seidman, Steven J.M. Jones, Hsu Chao, Candance Shelton, Carmen Gomez-Fernandez, Carrie Sougnez, Piotr A. Mieczkowski, Lee Lichtenstein, Erik Zmuda, Johanna Gardner, Jianjiong Gao, Marco A. Marra, Juok Cho, Alexei Protopopov, Roy Tarnuzzer, Tod D. Casasent, Timothy M. Chan, Michael Parfenov, Jing Wang, Christine M. Komarck, Lauren Averett Byers, Rehan Akbani, Todd Pihl, Curtis R. Pickering, Aaron D. Tward, Chandra Sekhar Pedamallu, Han Si, Jan F. Prins, Vonn Walter, Simion I. Chiosea, Jacqueline E. Schein, James Stephen Marron, Ariane Nguyen, William W. Shockley, Jennifer R. Grandis, Zhining Wang, Jeffrey N. Myers, Konstanty Korski, Bradley A. Ozenberger, Margaret L. Gulley, Barry S. Taylor, B. Arman Aksoy, Ni Zhao, Ashley H. Salazar, Petar Stojanov, Tara M. Lichtenberg, Chu Chen, Donghui Tan, Bhishamjit S. Chera, Andrzej Mackiewicz, A. Gordon Robertson, Ronglai Shen, Lisa Wise, Charles M. Perou, Michael Mayo, Charles Saller, Timothy J. Triche, Dong Zeng, Yan Guo, Lixia Diao, Jonathan B. McHugh, Zhixiang Zuo, Gad Getz, John A. Demchok, Raja R. Seethala, Gordon Saksena, Liu Xi, Liming Yang, Justin A. Bishop, Jessica Walton, Greg Eley, Jessica Frick, John N. Weinstein, Kevin Lau, Jianhua Zhang, Kenna R. Mills Shaw, Miruna Balasundaram, Zubair Khan, Umadevi Veluvolu, Stuart R. Jefferys, Christie Kovar, Moiz S. Bootwalla, Rebecca Carlsen, Daniel Crain, Fei-Fei Liu, Matthiew Ibbs, Michael S. Noble, William K. Funkhouser, Shaowu Meng, Mei Huang, Ann Marie Egloff, George E. Sandusky, Yi Han, Eric S. Lander, Sam Ng, William Lee, Christina Yau, Reanne Bowlby, Erin Curley, Donna M. Muzny, Lynda Chin, Joel S. Parker, Stephen B. Baylin, Peter S. Hammerman, Julie Ahn, Christopher C. Benz, Benjamin Gross, Paul M. Weinberger, Gideon Dresdner, Luc G. T. Morris, Zhong Chen, You Hong Fan, Angeliki Pantazi, David I. Heiman, Bartosz Szybiak, Sahil Seth, Richard A. Gibbs, Trevor Hackman, Peggy Yena, Richard A. Moore, Darshan Singh, Yaron S.N. Butterfield, Andrew D. Cherniack, Jeffrey S. Moyer, Robert A. Burton, Peter J. Park, Rameen Beroukhim, Ricardo Ramirez, Natalia Issaeva, Michael S. Lawrence, Wen-Bin Liu, Xiaojia Ren, Chris Sander, Yunhu Wan, Daryl Waggott, Joseph A. Califano, David A. Pot, Mathew G. Soloway, Roni J. Bollag, Stacey Gabriel, Jeffrey S. Reid, Netty Santoso, Elizabeth Buda, Doug Voet, Xingzhi Song, Kyle Chang, Joseph Paulauskis, Thomas M. Harris, Jaegil Kim, Alan P. Hoyle, Marc Ladanyi, Anthony Saleh, Mark C. Weissler, Scott L. Carter, Kai Wang, Jonathan G. Seidman, Corbin D. Jones, Wojciech Golusiński, Robert Penny, Margi Sheth, and Lori Boice
Subjects: Cervical Cancer, Genome, head and neck, Cancer Genome Atlas Network, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Papillomaviridae, Aetiology, Genetics, Multidisciplinary, biology, HPV infection, virus diseases, Biological Sciences, integration sites, female genital diseases and pregnancy complications, Gene Expression Regulation, Neoplastic, Infectious Diseases, Head and Neck Neoplasms, DNA methylation, Host-Pathogen Interactions, HIV/AIDS, Infection, Human, Virus Integration, Molecular Sequence Data, DNA sequencing, Rare Diseases, medicine, Humans, cancer, Dental/Oral and Craniofacial Disease, Gene, genome rearrangement, Neoplastic, Base Sequence, Genome, Human, Human Genome, DNA Methylation, biology.organism_classification, medicine.disease, Human genetics, Gene Expression Regulation, Genes, Neoplasm, Sexually Transmitted Infections, Human genome, Genes, Neoplasm, papilloma virus
Abstract: Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.
Published: 2014

10. The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

Author: Caleb F. Davis, Christopher J. Ricketts, Min Wang, Lixing Yang, Andrew D. Cherniack, Hui Shen, Christian Buhay, Hyojin Kang, Sang Cheol Kim, Catherine C. Fahey, Kathryn E. Hacker, Gyan Bhanot, Dmitry A. Gordenin, Andy Chu, Preethi H. Gunaratne, Michael Biehl, Sahil Seth, Benny A. Kaipparettu, Christopher A. Bristow, Lawrence A. Donehower, Eric M. Wallen, Angela B. Smith, Satish K. Tickoo, Pheroze Tamboli, Victor Reuter, Laura S. Schmidt, James J. Hsieh, Toni K. Choueiri, A. Ari Hakimi, Lynda Chin, Matthew Meyerson, Raju Kucherlapati, Woong-Yang Park, A. Gordon Robertson, Peter W. Laird, Elizabeth P. Henske, David J. Kwiatkowski, Peter J. Park, Margaret Morgan, Brian Shuch, Donna Muzny, David A. Wheeler, W. Marston Linehan, Richard A. Gibbs, W. Kimryn Rathmell, Chad J. Creighton, Sabina Signoretti, Christopher Ricketts, Michael Seiler, Hsu Chao, Mike Dahdouli, Liu Xi, Nipun Kakkar, Jeffrey G. Reid, Brittany Downs, Jennifer Drummond, Donna Morton, Harsha Doddapaneni, Lora Lewis, Adam English, Qingchang Meng, Christie Kovar, Qiaoyan Wang, Walker Hale, Alicia Hawes, Divya Kalra, Kimberly Walker, Bradley A. Murray, Carrie Sougnez, Gordon Saksena, Scott L. Carter, Steven E. Schumacher, Barbara Tabak, Travis I. Zack, Gad Getz, Rameen Beroukhim, Stacey B. Gabriel, Adrian Ally, Miruna Balasundaram, Inanc Birol, Denise Brooks, Yaron S.N. Butterfield, Eric Chuah, Amanda Clarke, Noreen Dhalla, Ranabir Guin, Robert A. Holt, Katayoon Kasaian, Darlene Lee, Haiyan I. Li, Emilia Lim, Yussanne Ma, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Tina Wong, Steven J.M. Jones, Marco A. Marra, J. Todd Auman, Donghui Tan, Shaowu Meng, Corbin D. Jones, Katherine A. Hoadley, Piotr A. Mieczkowski, Lisle E. Mose, Stuart R. Jefferys, Jeffrey Roach, Umadevi Veluvolu, Matthew D. Wilkerson, Scot Waring, Elizabeth Buda, Junyuan Wu, Tom Bodenheimer, Alan P. Hoyle, Janae V. Simons, Mathew G. Soloway, Saianand Balu, Joel S. Parker, D. Neil Hayes, Charles M. Perou, Daniel J. Weisenberger, Moiz S. Bootwalla, Timothy Triche, Phillip H. Lai, David J. Van Den Berg, Stephen B. Baylin, Fengju Chen, Cristian Coarfa, Michael S. Noble, Daniel DiCara, Hailei Zhang, Juok Cho, David I. Heiman, Nils Gehlenborg, Doug Voet, Pei Lin, Scott Frazer, Petar Stojanov, Yingchun Liu, Lihua Zou, Jaegil Kim, Michael S. Lawrence, Alexei Protopopov, Xingzhi Song, Jianhua Zhang, Angeliki Pantazi, Angela Hadjipanayis, Eunjung Lee, Lovelace J. Luquette, Semin Lee, Michael Parfenov, Netty Santoso, Jonathan Seidman, Andrew W. Xu, Junehawk Lee, Steven A. Roberts, Leszek J. Klimczak, David Fargo, Martin Lang, Yoon-La Choi, June-Koo Lee, Wenyi Wang, Yu Fan, Jaeil Ahn, Rehan Akbani, John N. Weinstein, David Haussler, Singer Ma, Amie Radenbaugh, Jingchun Zhul, Tara M. Lichtenberg, Erik Zmuda, Aaron D. Black, Benjamin Hanf, Nilsa C. Ramirez, Lisa Wise, Jay Bowen, Kristen M. Leraas, Tracy M. Hall, Julie M. Gastier-Foster, William G. Kaelin, Leigh Thorne, Lori Boice, Mei Huang, Cathy Vocke, James Peterson, Robert Worrell, Maria Merino, Bogdan A. Czerniak, Kenneth D. Aldape, Christopher G. Wood, Paul T. Spellman, Michael B. Atkins, John Cheville, R. Houston Thompson, Mark A. Jensen, Todd Pihl, Yunhu Wan, Brenda Ayala, Julien Baboud, Sudhakar Velaga, Jessica Walton, Jia Liu, Sudha Chudamani, Ye Wu, Margi Sheth, Kenna R. Mills Shaw, John A. Demchok, Tanja Davidsen, Liming Yang, Zhining Wang, Roy W. Tarnuzzer, Jiashan Zhang, Greg Eley, Ina Felau, Jean Claude Zenklusen, Carolyn M. Hutter, Mark S. Guyer, Bradley A. Ozenberger, Heidi J. Sofia, and Intelligent Systems
Subjects: Mitochondrial DNA, Cancer Research, DNA Copy Number Variations, Somatic cell, Chromophobe Renal Cell Carcinoma, DNA Mutational Analysis, Molecular Sequence Data, Chromophobe cell, Biology, DNA, Mitochondrial, Article, Chromosome Breakpoints, Chromosomes, Human, Humans, Exome, Promoter Regions, Genetic, Carcinoma, Renal Cell, Telomerase, Genetics, Base Sequence, Genome, Human, Point mutation, Cell Biology, DNA Methylation, Kidney Neoplasms, Oncology, Kataegis, DNA methylation, Chromosome Deletion, Transcriptome
Abstract: We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations.
Published: 2014

11. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

Author: Hoadley, Katherine A., Yau, Christina, Wolf, Denise M., Cherniack, Andrew D., Tamborero, David, Sam, Ng, Leiserson, Max D. M., Niu, Beifang, Mclellan, Michael D., Uzunangelov, Vladislav, Zhang, Jiashan, Kandoth, Cyriac, Akbani, Rehan, Shen, Hui, Omberg, Larsson, Chu, Andy, Margolin, Adam A., Van'T Veer, Laura J., Lopez Bigas, Nuria, Laird, Peter W., Raphael, Benjamin J., Ding, Li, Robertson, A. Gordon, Byers, Lauren A., Mills, Gordon B., Weinstein, John N., Van Waes, Carter, Chen, Zhong, Collisson, Eric A., Benz, Christopher C, Perou, Charles M., Stuart, Joshua M., Rachel, Abbott, Scott, Abbott, Arman Aksoy, B., Kenneth, Aldape, Adrian, Ally, Samirku mar Amin, Dimitris, Anastassiou, Todd Auman, J., Baggerly, Keith A., Miruna, Balasundaram, Saianand, Balu, Baylin, Stephen B., Benz, Stephen C., Berman, Benjamin P., Brady, Bernard, Bhatt, Ami S., Inanc, Birol, Black, Aaron D., Tom, Bodenheimer, Bootwalla, Moiz S., Jay, Bowen, Ryan, Bressler, Bristow, Christopher A., Brooks, Angela N., Bradley, Broom, Elizabeth, Buda, Robert, Burton, Butterfield, Yaron S. N., Daniel, Carlin, Carter, Scott L., Casasent, Tod D., Kyle, Chang, Stephen, Chanock, Lynda, Chin, Dong Yeon Cho, Juok, Cho, Eric, Chuah, Chun, Hye Jung E., Kristian, Cibulskis, Giovanni, Ciriello, James Cle land, Melisssa, Cline, Brian, Craft, Creighton, Chad J., Ludmila, Danilova, Tanja, Davidsen, Caleb, Davis, Dees, Nathan D., Kim, Delehaunty, Demchok, John A., Noreen, Dhalla, Daniel, Dicara, Huyen, Dinh, Dobson, Jason R., Deepti, Dodda, Harshavardhan, Doddapaneni, Lawrence, Donehower, Dooling, David J., Gideon, Dresdner, Jennifer, Drummond, Andrea, Eakin, Mary, Edgerton, Eldred, Jim M., Greg, Eley, Kyle, Ellrott, Cheng, Fan, Suzanne, Fei, Ina, Felau, Scott, Frazer, Freeman, Samuel S., Jessica, Frick, Fronick, Catrina C., Ful ton, Lucinda L., Robert, Fulton, Gabriel, Stacey B., Jianjiong, Gao, Gastier Foster, Julie M., Nils, Gehlenborg, Myra, George, Gad, Getz, Richard, Gibbs, Mary, Goldman, Abel Gonzalez Perez, Benjamin, Gross, Ranabir, Guin, Preethi, Gunaratne, Angela, Hadjipanayis, Hamilton, Mark P., Hamilton, Stanley R., Leng, Han, Han, Yi, Harper, Hollie A., Psalm, Haseley, David, Haussler, Neil Hayes, D., Heiman, David I., Elena, Helman, Carmen, Helsel, Herbrich, Shelley M., Her man, James G., Toshinori, Hinoue, Carrie, Hirst, Martin, Hirst, Holt, Robert A., Hoyle, Alan P., Lisa, Iype, Anders, Jacobsen, Jeffreys, Stuart R., Jensen, Mark A., Jones, Corbin D., Jones, Steven J. M., Zhenlin, Ju, Joonil, Jung, Andre, Kahles, Ari, Kahn, Joelle Kalicki Veizer, Divya, Kalra, Krishna Latha Kanchi, Kane, David W., Hoon, Kim, Jaegil, Kim, Theo, Knijnenburg, Koboldt, Daniel C., Christie, Kovar, Roger, Kramer, Richard, Kreisberg, Raju, Kucherlapati, Marc, Ladanyi, Lander, Eric S., Larson, David E., Lawrence, Michael S., Darlene, Lee, Eunjung, Lee, Semin, Lee, William, Lee, Kjong Van Lehmann, Kalle, Leinonen, Ler aas, Kristen M., Seth, Lerner, Levine, Douglas A., Lora, Lewis, Ley, Timothy J., Haiyan I., Li, Jun, Li, Wei, Li, Han, Liang, Lichtenberg, Tara M., Jake, Lin, Ling, Lin, Pei, Lin, Wen bin Liu, Yingchun, Liu, Yuexin, Liu, Lorenzi, Philip L., Charles, Lu, Yiling, Lu, Luquette, Love lace J., Singer, Ma, Magrini, Vincent J., Mahadeshwar, Harshad S., Mardis, Elaine R., Adam, Margolin, Marra, Marco A., Michael, Mayo, Cynthia, Mcallister, Mcguire, Sean E., Mcmichael, Joshua F., James, Melott, Shaowu, Meng, Matthew, Meyerson, Mieczkowski, Piotr A., Miller, Christopher A., Miller, Martin L., Michael, Miller, Moore, Richard A., Margaret, Morgan, Donna, Morton, Mose, Lisle E., Mungall, Andrew J., Donna, Muzny, Lam, Nguyen, Noble, Michael S., Houtan, Noushmehr, Michelle, O’Laughlin, Ojesina, Akinyemi I., Tai Hsien Ou Yang, Brad, Ozenberger, Angeliki, Pantazi, Michael, Parfenov, Park, Peter J., Parker, Joel S., Evan, Paull, Chandra Sekhar Pedamallu, Todd, Pihl, Craig, Pohl, David, Pot, Alexei, Protopopov, Teresa, Przytycka, Amie Raden baugh, Ramirez, Nilsa C., Ricardo, Ramirez, Gunnar Ra, ̈ tsch, Jeffrey, Reid, Xiao jia Ren, Boris, Reva, Reynolds, Sheila M., Rhie, Suhn K., Jeffrey, Roach, Hector, Rovira, Michael, Ryan, Gordon, Saksena, Sofie, Salama, Chris, Sander, Netty, Santoso, Schein, Jacqueline E., Heather, Schmidt, Nikolaus, Schultz, Schumacher, Steven E., Jonathan, Seidman, Yasin, Senbabaoglu, Sahil, Seth, Saman tha Sharpe, Ronglai, Shen, Margi, Sheth, Yan, Shi, Ilya, Shmulevich, Silva, Grace O., Simons, Janae V., Rileen, Sinha, Payal, Sipahimalani, Smith, Scott M., Sofia, Heidi J., Artem, Sokolov, Soloway, Mathew G., Xingzhi, Song, Carrie Soug nez, Paul, Spellman, Louis, Staudt, Chip, Stewart, Petar, Stojanov, Xiaoping, Su, Onur Sumer, S., Yichao, Sun, Teresa, Swatloski, Barbara, Tabak, Angela, Tam, Donghui, Tan, Jiabin, Tang, Roy, Tarnuzzer, Taylor, Barry S., Nina, Thiessen, Ves teinn Thorsson, Timothy Triche, J. r., Van Den Berg, David J., Vandin, Fabio, Varhol, Richard J., Vaske, Charles J., Umadevi, Veluvolu, Roeland, Verhaak, Doug, Voet, Jason, Walker, Wallis, John W., Peter, Waltman, Yunhu, Wan, Min, Wang, Wenyi, Wang, Zhining, Wang, Scot, Waring, Nils, Weinhold, Weisenberger, Daniel J., Wendl, Michael C., David, Wheeler, Wilkerson, Matthew D., Wilson, Richard K., Lisa, Wise, Andrew, Wong, Chang Jiun Wu, Chia Chin Wu, Hsin Ta Wu, Junyuan, Wu, Todd, Wylie, Liu, Xi, Ruibin, Xi, Zheng, Xia, Andrew W., Xu, Yang, Da, Liming, Yang, Lixing, Yang, Yang, Yang, Jun, Yao, Rong, Yao, Kai, Ye, Ko suke Yoshihara, Yuan, Yuan, Yung, Alfred K., Travis, Zack, Dong, Zeng, Jean Claude Zenklusen, Hailei, Zhang, Jianhua, Zhang, Nianxiang, Zhang, Qunyuan, Zhang, Wei, Zhang, Wei, Zhao, Siyuan, Zheng, Jing, Zhu, Erik, Zmuda, and Lihua, Zou
Subjects: Genetics and Molecular Biology (all), Cluster Analysis, Humans, Neoplasms, Transcriptome, Biochemistry, Genetics and Molecular Biology (all), Extramural, Biochemistry, Genetics and Molecular Biology(all), Cancer, Computational biology, Disease, Biology, medicine.disease, Bioinformatics, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Article, 3. Good health, Molecular classification, TP63, CLUSTERS (ANÁLISE), medicine, Head and neck, Gene
Abstract: Summary Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.
Published: 2014
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12. The Cancer Genome Atlas Pan-Cancer analysis project

Author: Qunyuan Zhang, B. Arman Aksoy, Fabio Vandin, Eric A. Collisson, Larsson Omberg, S. Onur Sumer, John A. Demchok, Sven Nelander, Vladislav Uzunangelov, Michael C. Wendl, Roger Kramer, John W. Wallis, Brian Craft, Angeliki Pantazi, Leng Han, W. K. Alfred Yung, Brad Ozenberger, Philip L. Lorenzi, James G. Herman, Andy Chu, Sahil Seth, Richard A. Gibbs, Angela Hadjipanayis, Hector Rovira, Peter W. Laird, Inanc Birol, Richard K. Wilson, James Cleland, Peter J. Park, Jiashan Zhang, Payal Sipahimalani, Stanley R. Hamilton, Liming Yang, Seth Lerner, Amie Radenbaugh, Barry S. Taylor, Carrie Hirst, David Tamborero, Stephen B. Baylin, Gad Getz, Tanja Davidsen, Miruna Balasundaram, Cheng Fan, Yuan Yuan, Kristian Cibulskis, Yan Shi, Angela Tam, Divya Kalra, Chris Sander, Scott Abbott, Catrina Fronick, Margi Sheth, Chip Stewart, Angela N. Brooks, Noreen Dhalla, Lam Nguyen, Hui Shen, Travis I. Zack, Andrew J. Mungall, Artem Sokolov, Douglas A. Levine, Carrie Sougnez, Paul T. Spellman, Greg Eley, Deepti Dodda, Wenbin Liu, Michael B. Ryan, Liu Xi, Aaron D. Black, Rong Yao, Saianand Balu, Benjamin P. Berman, Raju Kucherlapati, James M. Melott, Xingzhi Song, Boris Reva, Huyen Dinh, David A. Pot, Michael D. McLellan, Kjong-Van Lehmann, Wenyi Wang, Petar Stojanov, Bradley McIntosh Broom, Timothy J. Ley, Da Yang, Mary Elizabeth Edgerton, Houtan Noushmehr, Mathew G. Soloway, Nina Thiessen, Zhenlin Ju, Mark D.M. Leiserson, Michael Parfenov, Laura van 't Veer, Scott L. Carter, Ludmila Danilova, Adrian Ally, Hailei Zhang, Ina Felau, Carmen Helsel, Kenneth Aldape, Teresia Kling, Charles Lu, Psalm Haseley, A. Gordon Robertson, Andrew Wei Xu, Jessica Frick, Benjamin Gross, Louis M. Staudt, Craig Pohl, Dimitris Anastassiou, Netty Santoso, Donna Muzny, Chad J. Creighton, Donghui Tan, Ryan Bressler, Andrew J. Wong, Barbara Tabak, Yasin Senbabaoglu, Daniel C. Koboldt, Darlene Lee, Doug Voet, Joonil Jung, Hollie A. Harper, Jianhua Zhang, Kyle Chang, Wei Zhao, Marc Ladanyi, Lisa Iype, Ricardo Ramirez, Ami S. Bhatt, Lisle E. Mose, Singer Ma, Abel Gonzalez-Perez, Jonathan G. Seidman, Kosuke Yoshihara, Denise M. Wolf, Corbin D. Jones, Patrik Johansson, Siyuan Zheng, André Kahles, Stacey Gabriel, John N. Weinstein, Han Liang, Samantha Sharpe, Steven E. Schumacher, Matthew Meyerson, D. Neil Hayes, David Haussler, Krishna L. Kanchi, Julie M. Gastier-Foster, Umadevi Veluvolu, Ari B. Kahn, Brady Bernard, Tod D. Casasent, Christopher A. Bristow, Akinyemi I. Ojesina, Sam Ng, Charles M. Perou, Moiz S. Bootwalla, Cyriac Kandoth, Lixing Yang, Joel S. Parker, Alan P. Hoyle, Timothy J. Triche, Dong Zeng, Sean E. McGuire, Christie Kovar, Kim D. Delehaunty, Juok Cho, Alexei Protopopov, Shaowu Meng, Ling Lin, Heather Schmidt, Nils Gehlenborg, Yuexin Liu, Elaine R. Mardis, Martin L. Miller, Jake Lin, Jason Walker, Lisa Wise, Suzanne S. Fei, Jacqueline E. Schein, Semin Lee, Christina Yau, Melisssa Cline, Tara M. Lichtenberg, David I. Heiman, Scot Waring, Richard A. Moore, Margaret B. Morgan, Robert S. Fulton, David E. Larson, Xiaoping Su, Kalle Leinonen, Samirkumar B. Amin, Joshua M. Stuart, J. Todd Auman, Rebecka Jörnsten, Rileen Sinha, Andrew D. Cherniack, Caleb F. Davis, Stephen J. Chanock, Nathan D. Dees, Adam Margolin, Haiyan I. Li, Yaron S.N. Butterfield, Daniel E. Carlin, Tai Hsien Ou Yang, Rameen Beroukhim, Vincent Magrini, Mark P. Hamilton, Grace O. Silva, Nils Weinhold, Harshad S. Mahadeshwar, Michael S. Lawrence, Eric Chuah, Jun Li, Wei Li, Robert A. Burton, Teresa M. Przytycka, Katherine A. Hoadley, Keith A. Baggerly, Sheila M. Reynolds, Daniel DiCara, Tom Bodenheimer, Charles J. Vaske, James M. Eldred, Richard Varhol, Mark A. Jensen, David W. Kane, Xiaojia Ren, Christopher A. Miller, Elizabeth Buda, Li Ding, Michael Mayo, Hsin-Ta Wu, Joelle Kalicki-Veizer, Shelley M. Herbrich, Eunjung Lee, Yingchun Liu, Joshua F. McMichael, Jennifer Drummond, Teresa Swatloski, Harshavardhan Doddapaneni, William Lee, Daniel J. Weisenberger, David A. Wheeler, Chia Chin Wu, Richard Kreisberg, Roeland Verhaak, Elena Helman, Piotr A. Mieczkowski, Mary Goldman, Ilya Shmulevich, Nikolaus Schultz, Min Wang, Lovelace J. Luquette, Marco A. Marra, Todd Pihl, Roy Tarnuzzer, Ronglai Shen, Donna Morton, Yichao Sun, Lawrence A. Donehower, Jun Yao, Theo A. Knijnenburg, Benjamin J. Raphael, Lora Lewis, Peter Waltman, Andrea Eakin, Martin Hirst, Jaegil Kim, Lihua Zou, Ranabir Guin, Yi Han, Scott M. Smith, Hoon Kim, Kristen M. Leraas, Heidi J. Sofia, Erik Zmuda, Matthew D. Wilkerson, Michelle O'Laughlin, Jianjiong Gao, Jeffrey G. Reid, Jing Zhu, Toshinori Hinoue, Gunnar Rätsch, Hye Jung E. Chun, Anders Jacobsen, Stephen C. Benz, Kenna R. Mills Shaw, Gordon B. Mills, Zhining Wang, Cynthia McAllister, Michael S. Noble, Christopher C. Benz, Rehan Akbani, Ruibin Xi, Nianxiang Zhang, Jay Bowen, Wei Zhang, Chandra Sekhar Pedamallu, Eric S. Lander, Yunhu Wan, David J. Dooling, Dong Yeon Cho, Preethi Gunaratne, Todd Wylie, Pei Lin, Chang-Jiun Wu, Jeffrey Roach, Scott Frazer, Samuel S. Freeman, Rachel Abbott, Zheng Xia, Lucinda Fulton, Kyle Ellrott, Nuria Lopez-Bigas, Yang Yang, Michael Miller, Nilsa C. Ramirez, Evan O. Paull, Janae V. Simons, Junyuan Wu, Lynda Chin, Gordon Saksena, Jiabin Tang, Vesteinn Thorsson, Robert A. Holt, Suhn K. Rhie, Steven J.M. Jones, Stuart R. Jeffreys, Giovanni Ciriello, Sofie R. Salama, Gideon Dresdner, Yiling Lu, Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., and Park, Peter J.
Subjects: Genetics, medicine.medical_specialty, Genome, Gene Expression Profiling, Genomics, Computational biology, Biology, Humans, Neoplasms, Article, Analysis Project, Gene expression profiling, GENÉTICA MOLECULAR, Cancer genome, Genomic Profile, medicine, Medical genetics, Epigenetics
Abstract: The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile., National Cancer Institute (U.S.), National Human Genome Research Institute (U.S.)
Published: 2013

13. Comprehensive molecular characterization of urothelial bladder carcinoma

Author: Elizabeth Buda, Nikolaus Schultz, Donghui Tan, Pat Swanson, Xingzhi Song, Jennifer Owens, Carmelo Gaudioso, Liming Yang, Kenna R. Mills Shaw, Sophie C. Egea, John N. Weinstein, Lihua Zou, Dmitry A. Gordenin, Gad Getz, Stuart R. Jefferys, Wiam Bshara, David Haussler, Ari B. Kahn, Mary Iacocca, Brady Bernard, Charles M. Perou, Leigh B. Thorne, Kimberly R. Christ, Eric S. Lander, Yunhu Wan, Timothy J. Triche, Dong Zeng, Bogdan Czerniak, Wenbin Liu, Jianhua Zhang, David Mallery, B. Arman Aksoy, Lynn M. Herbert, Hailei Zhang, Jennifer DiPiero, Tod D. Casasent, Sugy Kodeeswaran, Daniel DiCara, Jacqueline E. Schein, Scott L. Carter, Umadevi Veluvolu, John M. S. Bartlett, Theresa M. Koppie, Ji Yeon Yang, Ronglai Shen, Yingchun Liu, Daniel J. Weisenberger, Ranabir Guin, Myra M. George, Marc Ladanyi, J. Todd Auman, Moiz S. Bootwalla, Shaowu Meng, Mark S. Soloway, Tatjana Antic, Greg Eley, Hikmat Al-Ahmadie, Carolyn M. Hutter, Jonathan G. Seidman, Corbin D. Jones, Lori Boice, Xiaoping Su, Jay Bowen, Raju Kucherlapati, Hui Shen, Benjamin Gross, Reanne Bowlby, Lawrence A. Donehower, Phan Thi Hanh, David J. McConkey, Saianand Balu, Jiexin Zhang, Tina Wong, Juok Cho, Alexei Protopopov, Carolyn L. Smith, Yuexin Liu, Angeliki Pantazi, Jason R. Gee, Xuan Van Le, Ricardo Ramirez, Ami S. Bhatt, Samuel S. Freeman, Jaegil Kim, Bui Duc Phu, Michael Ittman, Charles C. Guo, Carmen Gomez-Fernandez, Norm D. Smith, S. Onur Sumer, Bradley A. Ozenberger, Paul M. Weinberger, George E. Sandusky, Troy Shelton, Seth P. Lerner, Charles Saller, Nicholas J. Petrelli, Nguyen Van Bang, Sahil Seth, Richard A. Gibbs, Lisle E. Mose, Aaron D. Black, Yair Lotan, Carrie Sougnez, Jessie Au, Martin L. Ferguson, Ashley Marie Regazzi, Matthew Meyerson, Joel B. Nelson, Natasja Wye, Daniel E. Carlin, Nils Weinhold, Tom Bodenheimer, Nilsa C. Ramirez, Michael Ryan, Anders Jacobsen, Eric J. Burks, Lee Lichtenstein, Erin Curley, Angela Hadjipanayis, Nils Gehlenborg, Hector Rovira, Bernard Kohl, Jean C. Zenklusen, Travis Sullivan, Margaret Morgan, Rajiv Dhir, Julie M. Gastier-Foster, Gary D. Steinberg, Mathew G. Soloway, Nina Thiessen, Jianjiong Gao, Lisa Wise, Barry S. Taylor, Gordon Saksena, Hui Yao, David Van Den Berg, Jiabin Tang, Robert Penny, Nguyen Viet Tien, Jeffrey R. Gingrich, Jing Zhu, Ronald L. Hrebinko, Dick Kreisberg, Pei Lin, Christopher A. Bristow, Andrey Sivachenko, Andy Chu, Peter W. Laird, Thomas Barr, Junyuan Wu, Robert A. Holt, Harshad S. Mahadeshwar, Piotr A. Mieczkowski, Steven A. Roberts, Victor E. Reuter, Jeffrey S. Damrauer, Roni J. Bollag, Chad J. Creighton, Johanna Gardner, Michael Parfenov, Qiang Li, Phillip H. Lai, Thomas C. Motter, Alireza Moinzadeh, Jodi K. Maranchie, Christopher C. Benz, Lynda Chin, Angela Tam, Margi Sheth, David B. Solit, Erik Zmuda, Lixing Yang, Peter J. Park, Marco A. Marra, Katherine A. Hoadley, Eila C. Skinner, Scott Frazer, Roy Tarnuzzer, Heidi J. Sofia, Bradley M. Broom, Zhining Wang, David I. Heiman, Sebrina A Tello, Lori Huelsenbeck-Dill, Steven J.M. Jones, Antonia H. Holway, Ilana Rebecca Garcia-Grossman, Merce Jorda, Roeland Verhaak, Ilya Shmulevich, W.K. Rathmell, Bernard H. Bochner, Scot Waring, Kenneth Aldape, Richard A. Moore, Toshinori Hinoue, Carrie Hirst, Mark A. Jensen, Payal Kapur, Andrew D. Cherniack, Dean F. Bajorin, Evano Paull, Cheryl M. Lewis, William Y. Kim, Giovanni Ciriello, David C. Fargo, Gordon B. Mills, Michael S. Noble, Stephanie Weaver, Whitney D. McClenden, Benjamin Davies, Payal Sipahimalani, Vina Alexopoulou, Bo Peng, Stephen B. Baylin, Michael Mayo, Rameen Beroukhim, Boris Reva, Anil V. Parwani, Joshua M. Stuart, David J. Kwiatkowski, Stacey B. Gabrie, Janae V. Simons, Rehan Akbani, Todd Pihl, Nianxiang Zhang, Suzie Carter, Michael S. Lawrence, Carmen Helsel, Carl Morrison, Xiaojia Ren, Jeffrey Roach, Peter H. O'Donnell, Miruna Balasundaram, Yevgeniy Antipin, Gideon Dresdner, Cynthia McAllister, Tanja Davidsen, Brenda Rabeno, Jolanta Bondaruk, Kristian Cibulskis, Chip Stewart, Matthew D. Wilkerson, Jonathan E. Rosenberg, Brian D. Robinson, Patricia Castro, Wei Zhang, Chandra Sekhar Pedamallu, Allison Beaver, Andrew Wei Xu, Adrian Ally, Andrea Sorcini, Andrew J. Mungall, Katherine Tarvin, Christine Czerwinski, Petar Stojanov, Philip L. Lorenzi, Alan P. Hoyle, Jay Engel, Tara M. Lichtenberg, D. Neil Hayes, John A. Demchok, Eric Chuah, Benjamin Hanf, Deepak Srinivasan, Donna E. Hansel, Noreen Dhalla, Zhenlin Ju, Leszek J. Klimczak, Trevor J. Pugh, Richard Thorp, A. Gordon Robertson, Darlene Lee, Steven E. Schumacher, Semin Lee, Sheldon I. Bastacky, Rileen Sinha, Haiyan I. Li, William Lee, Sam Ng, Joel S. Parker, Sheila Reynolds, Teresa R. Tabler, Yaron S.N. Butterfield, David Pot, Chris Sander, Wenyi Wang, Weiguo Jian, Le Quang Vinh, Netty Santoso, Doug Voet, and Joonil Jung
Subjects: Metastatic Urothelial Carcinoma, Invasive urothelial carcinoma, Virus Integration, Down-Regulation, Disease, Bioinformatics, Malignancy, Article, Phosphatidylinositol 3-Kinases, Cancer genome, medicine, Carcinoma, Humans, Molecular Targeted Therapy, RNA, Messenger, Urothelial carcinoma, Multidisciplinary, business.industry, TOR Serine-Threonine Kinases, Cell Cycle, Creative commons, medicine.disease, Chromatin, 3. Good health, Gene Expression Regulation, Neoplastic, MicroRNAs, Oxidative Stress, Urinary Bladder Neoplasms, business, Protein Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract: Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.
Published: 2013

14. Comprehensive molecular profiling of lung adenocarcinoma

Author: Amie Radenbaugh, Noreen Dhalla, Christina Williamson, Charles Saller, James Suh, Ramaswamy Govindan, Travis I. Zack, Paul T. Spellman, Daniel DiCara, Harvey I. Pass, Deepak Srinivasan, William G. Richards, Robert J. Cerfolio, Igor Letovanec, A. Gordon Robertson, Gabriel Sica, Chad J. Creighton, Hendrik Dienemann, Jeffrey A. Borgia, Boris Reva, Bryan F. Meyers, Yiling Lu, Nikolaus Schultz, Christopher I. Amos, Dante Trusty, Carmelo Gaudioso, Michael Meister, James T. Robinson, Lihua Zou, James Shin, Jeremy Parfitt, Darlene Lee, Junyuan Wu, Carl Morrison, Scott L. Carter, Giovanni Ciriello, Nils Weinhold, Elena Nemirovich-Danchenko, Andrew Wei Xu, Christopher G. Maher, Lori Boice, Irina Zaytseva, Dennis A. Wigle, Kenna R. Mills Shaw, Matthew G. Soloway, Matthew Meyerson, Peng Chieh Chen, Frank Schneider, Troy Shelton, Douglas Voet, Steven E. Schumacher, D L Rotin, Saianand Balu, Stuart R. Jefferys, Tom Bodenheimer, Bradley A. Ozenberger, Eric S. Lander, Edward Gabrielson, Konstantin V. Fedosenko, Rehan Akbani, William D. Travis, Ari B. Kahn, Marcin Imielinski, Jacqueline E. Schein, Thomas L. Bauer, Kai Ye, Samuel A. Yousem, Robert C. Onofrio, Thomas Muley, Ayesha S. Bryant, Michael K. Asiedu, Monique Albert, Pei Lin, Corbin D. Jones, Edwina Duhig, Jean C. Zenklusen, Lucinda Fulton, Christina Yau, J. Todd Auman, Leigh B. Thorne, Elena Helman, Richard T. Cheney, William Lee, Patrick K. Kimes, Juok Cho, Alexei Protopopov, Wenbin Liu, Lee Lichtenstein, Jing Wang, Lixing Yang, W. Kimryn Rathmell, Jo Ellen Weaver, David A. Wheeler, Leslie Cope, Mark A. Watson, Heidi J. Sofia, Angeliki Pantazi, Ronglai Shen, Jeffrey Roach, Eric A. Collisson, Patrick Kwok Shing Ng, Angela Hadjipanayis, Peter S. Hammerman, David Van Den Berg, Kwun M. Fong, Nils Gehlenborg, Natasha Rekhtman, William K. Funkhouser, D. Neil Hayes, Harshad S. Mahadeshwar, Semin Lee, Martin Peifer, David Mallery, Piotr A. Mieczkowski, Ranabir Guin, Madhusmita Behera, Philipp A. Schnabel, Jill M. Siegfried, Carmen Gomez-Fernandez, Johanna Gardner, Lynn M. Herbert, Hailei Zhang, Robert S. Fulton, Travis Sullivan, Sahil Seth, Sam Ng, Chandra Sekhar Pedamallu, Barry S. Taylor, Venkatraman E. Seshan, Valerie W. Rusch, Jinze Liu, Daniel P. Raymond, Jianjiong Gao, Nathan A. Pennell, Marco A. Marra, Jan F. Prins, Payal Sipahimalani, Janae V. Simons, Joel S. Parker, Rileen Sinha, Lindy Hunter, Raju Kucherlapati, Dennis T. Maglinte, Fedor Moiseenko, Eric E. Snyder, Roy Tarnuzzer, Beverly Lee, James Stephen Marron, Kristian Cibulskis, Jerome Myers, Haiyan I. Li, Robert Penny, Hartmut Juhl, Richard K. Wilson, Zhining Wang, Eran Hodis, Carrie Sougnez, Jiabin Tang, William Mallard, Bryan Hernandez, Liming Yang, Jennifer Brown, Gad Getz, Farhad Kosari, Catrina Fronick, Juliann Chmielecki, Jianhua Zhang, Suresh S. Ramalingam, Michael Parfenov, Peter J. Park, Tanja Davidsen, Philip H. Lai, Jeff Boyd, Dang Huy Quoc Thinh, Harmanjatinder S. Sekhon, Malcolm V. Brock, Mark Pool, Margi Sheth, Kimberly M. Rieger-Christ, Michael J. Liptay, E. Getz, S. Onur Sumer, Ian A. Yang, B. Arman Aksoy, Douglas B. Flieder, Bradley M. Broom, Carrie Hirst, Solange Peters, Joshua M. Stuart, Khurram Z. Khan, Scott Morris, Donghui Tan, Andrew J. Mungall, Ming-Sound Tsao, Gordon B. Mills, Stephen B. Baylin, Rebecca Carlsen, Sanja Dacic, Julien Baboud, Brenda Rabeno, Richard A. Hajek, Lauren Averett Byers, Yaron S.N. Butterfield, Miruna Balasundaram, Chip Stewart, Katherine Tarvin, Peter B. Illei, James G. Herman, David J. Kwiatkowski, Andy Chu, David Haussler, Natasja Wye, Charles M. Perou, Peter W. Laird, Timothy J. Triche, Yan Shi, Jill P. Mesirov, Angela N. Brooks, Lori Huelsenbeck-Dill, Steven J.M. Jones, Antonia H. Holway, Lixia Diao, Anthony A. Gal, David G. Beer, Angela Tam, Ashley H. Salazar, Mark A. Jensen, Robert A. Holt, Katherine A. Hoadley, John A. Demchok, Sandra McDonald, Chandra Goparaju, David Pot, Belinda E. Clarke, Gordon Robertson, Michael C. Wendl, Helga Thorvaldsdottir, Kristen Rogers, Joshua D. Campbell, Chris Sander, Rayleen V. Bowman, Marc Danie Nazaire, Michael Mayo, Olga Voronina, Ludmila Danilova, Paul Zippile, Netty Santoso, John V. Heymach, Matthew D. Wilkerson, John Eckman, Morgan Windsor, Cureline Oleg Dolzhanskiy, Nina Thiessen, Mara Rosenberg, Gideon Dresdner, Levi A. Garraway, Eric Chuah, Richard Varhol, Elizabeth Buda, Li Ding, Alice H. Berger, Xingzhi Song, John M. S. Bartlett, Michael D. McLellan, Olga Potapova, Joseph Paulauskis, Igor Jurisica, Benjamin Gross, Jaegil Kim, John N. Weinstein, Kevin Lau, Christopher R. Cabanski, Philip Bonomi, Michael S. Noble, Maureen F. Zakowski, George E. Sandusky, Mary Iacocca, Eric J. Burks, Erin Curley, Lynda Chin, Rajiv Dhir, Singer Ma, Sophie C. Egea, Umadevi Veluvolu, Sugy Kodeeswaran, Christopher A. Miller, Moiz S. Bootwalla, Daniel J. Weisenberger, Shaowu Meng, Mei Huang, Elaine R. Mardis, Gordon Saksena, Nicholas J. Petrelli, Yvonne Owusu-Sarpong, Christopher C. Benz, Bernard Kohl, Jingchun Zhu, David I. Heiman, Carol Farver, Scot Waring, Richard A. Moore, Darshan Singh, Andrew D. Cherniack, Rameen Beroukhim, Michael S. Lawrence, Xiaojia Ren, Marc Ladanyi, Stacey Gabriel, Christine Czerwinski, Alan P. Hoyle, Cancer Genome Atlas Research Network, Collisson, E. A., Campbell, J.D., Brooks, A.N., Berger, A.H., Lee, W., Chmielecki, J., Beer, D.G., Cope, L., Creighton, C.J., Danilova, L., Ding, L., Getz, G., Hammerman, P.S., Hayes, D.N., Hernandez, B., Herman, J.G., Heymach, J.V., Jurisica, I., Kucherlapati, R., Kwiatkowski, D., Ladanyi, M., Robertson, G., Schultz, N., Shen, R., Sinha, R., Sougnez, C., Tsao, M.S., Travis, W.D., Weinstein, J.N., Wigle, D.A., Wilkerson, M.D., Chu, A., Cherniack, A.D., Hadjipanayis, A., Rosenberg, M., Weisenberger, D.J., Laird, P.W., Radenbaugh, A., Ma, S., Stuart, J.M., Averett Byers, L., Baylin, S.B., Govindan, R., Meyerson, M., Gabriel, S.B., Cibulskis, K., Kim, J., Stewart, C., Lichtenstein, L., Lander, E.S., Lawrence, M.S., Kandoth, C., Fulton, R., Fulton, L.L., McLellan, M.D., Wilson, R.K., Ye, K., Fronick, C.C., Maher, C.A., Miller, C.A., Wendl, M.C., Cabanski, C., Mardis, E., Wheeler, D., Balasundaram, M., Butterfield, Y.S., Carlsen, R., Chuah, E., Dhalla, N., Guin, R., Hirst, C., Lee, D., Li, H.I., Mayo, M., Moore, R.A., Mungall, A.J., Schein, J.E., Sipahimalani, P., Tam, A., Varhol, R., Robertson, A., Wye, N., Thiessen, N., Holt, R.A., Jones, S.J., Marra, M.A., Imielinski, M., Onofrio, R.C., Hodis, E., Zack, T., Helman, E., Sekhar Pedamallu, C., Mesirov, J., Saksena, G., Schumacher, S.E., Carter, S.L., Garraway, L., Beroukhim, R., Lee, S., Mahadeshwar, H.S., Pantazi, A., Protopopov, A., Ren, X., Seth, S., Song, X., Tang, J., Yang, L., Zhang, J., Chen, P.C., Parfenov, M., Wei Xu, A., Santoso, N., Chin, L., Park, P.J., Hoadley, K.A., Auman, J.T., Meng, S., Shi, Y., Buda, E., Waring, S., Veluvolu, U., Tan, D., Mieczkowski, P.A., Jones, C.D., Simons, J.V., Soloway, M.G., Bodenheimer, T., Jefferys, S.R., Roach, J., Hoyle, A.P., Wu, J., Balu, S., Singh, D., Prins, J.F., Marron, J.S., Parker, J.S., Perou, C.M., Liu, J., Maglinte, D.T., Lai, P.H., Bootwalla, M.S., Van Den Berg, D.J., Triche, T., Cho, J., DiCara, D., Heiman, D., Lin, P., Mallard, W., Voet, D., Zhang, H., Zou, L., Noble, M.S., Gehlenborg, N., Thorvaldsdottir, H., Nazaire, M.D., Robinson, J., Aksoy, B.A., Ciriello, G., Taylor, B.S., Dresdner, G., Gao, J., Gross, B., Seshan, V.E., Reva, B., Sumer, S.O., Weinhold, N., Sander, C., Ng, S., Zhu, J., Benz, C.C., Yau, C., Haussler, D., Spellman, P.T., Kimes, P.K., Broom, B.M., Wang, J., Lu, Y., Kwok Shing Ng, P., Diao, L., Liu, W., Amos, C.I., Akbani, R., Mills, G.B., Curley, E., Paulauskis, J., Lau, K., Morris, S., Shelton, T., Mallery, D., Gardner, J., Penny, R., Saller, C., Tarvin, K., Richards, W.G., Cerfolio, R., Bryant, A., Raymond, D.P., Pennell, N.A., Farver, C., Czerwinski, C., Huelsenbeck-Dill, L., Iacocca, M., Petrelli, N., Rabeno, B., Brown, J., Bauer, T., Dolzhanskiy, O., Potapova, O., Rotin, D., Voronina, O., Nemirovich-Danchenko, E., Fedosenko, K.V., Gal, A., Behera, M., Ramalingam, S.S., Sica, G., Flieder, D., Boyd, J., Weaver, J., Kohl, B., Huy Quoc Thinh, D., Sandusky, G., Juhl, H., Duhig, E., Illei, P., Gabrielson, E., Shin, J., Lee, B., Rodgers, K., Trusty, D., Brock, M.V., Williamson, C., Burks, E., Rieger-Christ, K., Holway, A., Sullivan, T., Asiedu, M.K., Kosari, F., Rekhtman, N., Zakowski, M., Rusch, V.W., Zippile, P., Suh, J., Pass, H., Goparaju, C., Owusu-Sarpong, Y., Bartlett, J.M., Kodeeswaran, S., Parfitt, J., Sekhon, H., Albert, M., Eckman, J., Myers, J.B., Cheney, R., Morrison, C., Gaudioso, C., Borgia, J.A., Bonomi, P., Pool, M., Liptay, M.J., Moiseenko, F., Zaytseva, I., Dienemann, H., Meister, M., Schnabel, P.A., Muley, T.R., Peifer, M., Gomez-Fernandez, C., Herbert, L., Egea, S., Huang, M., Thorne, L.B., Boice, L., Hill Salazar, A., Funkhouser, W.K., Rathmell, W.K., Dhir, R., Yousem, S.A., Dacic, S., Schneider, F., Siegfried, J.M., Hajek, R., Watson, M.A., McDonald, S., Meyers, B., Clarke, B., Yang, I.A., Fong, K.M., Hunter, L., Windsor, M., Bowman, R.V., Peters, S., Letovanec, I., Khan, K.Z., Jensen, M.A., Snyder, E.E., Srinivasan, D., Kahn, A.B., Baboud, J., Pot, D.A., Mills Shaw, K.R., Sheth, M., Davidsen, T., Demchok, J.A., Wang, Z., Tarnuzzer, R., Zenklusen, J.C., Ozenberger, B.A., Sofia, H.J., Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.
Subjects: Male, Lung Neoplasms, Adenocarcinoma/genetics, Adenocarcinoma/pathology, Cell Cycle Proteins/genetics, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Genomics, Humans, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Molecular Typing, Mutation/genetics, Oncogenes/genetics, Sex Factors, Transcriptome/genetics, Adenocarcinoma of Lung, Cell Cycle Proteins, Biology, Adenocarcinoma, Exon, Germline mutation, microRNA, Adenocarcinoma of the lung, medicine, Gene, Multidisciplinary, Oncogene, Oncogenes, medicine.disease, MET Exon 14 Skipping Mutation, Molecular biology, 3. Good health, Mutation, Transcriptome
Abstract: Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
Published: 2013

15. Comprehensive genomic characterization of squamous cell lung cancers

Author: Charles J. Vaske, Ying Du, Theodore C. Goldstein, Ping Yang, Yufeng Liu, Bryan Hernandez, Daniel R. Zerbino, Kenneth H. Buetow, Khurram Z. Khan, Semin Lee, Martin Peifer, Kristin G. Ardlie, James G. Herman, Sanja Dacic, Ashley Hill, Christopher Szeto, Jianjiong Gao, Singer Ma, Peng Chieh Chen, Carl F. Schaefer, David G. Beer, Kerstin David, Brent W. Zanke, Karen Mungall, Beverly Lee, Daniel DiCara, Kristen Rogers, Rui Jing, Christina Liquori, Carrie Sougnez, Ron Bose, Brian O'Connor, Piotr A. Mieczkowski, Scott L. Carter, Andy Chu, Peter W. Laird, David J. Kwiatkowski, R. Craig Cason, Marie Christine Aubry, Rileen Sinha, Dennis T. Maglinte, Chad J. Creighton, Howard H. Sussman, Jill M. Siegfried, Laura A.L. Dillon, Agnes Viale, Marco A. Marra, Stephen E. Schumacher, Dennis A. Wigle, Yongjun Zhao, Robert C. Onofrio, Heidi J. Sofia, Ranabir Guin, Lori Boice, Ling Li, Mark Backus, Pei Lin, Prachi Kothiyal, Jan F. Prins, Lauren Averett Byers, Haiyan I. Li, An He, Ka Ming Nip, Chang-Jiun Wu, Peter Dolina, James A. Robinson, Saianand Balu, Collisson E, Jinze Liu, Nicholas D. Socci, Erin Pleasance, Joan Pontius, Christina Yau, Eric E. Snyder, Shaowu Meng, Mei Huang, Aaron McKenna, Corbin D. Jones, Carl Morrison, Malcolm V. Brock, Chris Wakefield, Jared R. Slobodan, Ethan Cerami, Angela Tam, Jane Peterson, Michael D. Topal, Jacob M. Kaufman, Elena Helman, Richard T. Cheney, Dominik Stoll, Cristiane M. Ida, Dante Trusty, Peter S. Hammerman, Yevgeniy Antipin, D. Neil Hayes, Anders Jacobsen, Anna K. Unruh, Noreen Dhalla, Candace Shelton, Peter Waltman, Chris Sander, Zhining Wang, Derek Y. Chiang, Elizabeth J. Thomson, Vonn Walter, JoEllen Weaver, Elena Nemirovich-Danchenko, Jacqueline E. Schein, Bradley M. Broom, Sandra C. Tomaszek, Peter A. Kigonya, Tod D. Casasent, Ari B. Kahn, Joanne Yi, Kyle Ellrott, John M. S. Bartlett, Payal Sipahimalani, William D. Travis, Douglas Voet, Sean P. Barletta, Elizabeth Chun, J. Todd Auman, Ludmila Danilova, Katherine A. Hoadley, Marcin Imielinski, Ramaswamy Govindan, David P. Carbone, Leigh B. Thorne, David A. Wheeler, Carrie Hirst, Barbara Tabak, Sugy Kodeeswaran, Ijeoma A. Azodo, James Stephen Marron, Michael S. Noble, Jianjua John Zhang, Paul K. Paik, Deepak Srinivasan, Boris Reva, B. Arman Aksoy, Kristian Cibulskis, Douglas B. Flieder, Fei Pan, Daniel J. Weisenberger, Ronglai Shen, Jinhua Zhang, Nils Weinhold, Harman Sekhon, David Van Den Berg, Mark S. Guyer, Robert Penny, Hartmut Juhl, Marc Danie Nazaire, Yiqun Zhang, Eric A. Collisson, Robin J.N. Coope, Tom Bodenheimer, Richard Thorp, Junyuan Wu, Matthew Meyerson, Nguyen Phi Hung, Jerome Myers, Artem Sokolov, Yidi J. Turman, Thomas Muley, Stephen B. Baylin, Anisha Gulabani, A. Gordon Robertson, Lynda Chin, Eric Chuah, Richard Varhol, Margi Sheth, Janae V. Simons, Nils Gehlenborg, Tanja Davidsen, Psalm Haseley, Miruna Balasundaram, Olga Potapova, Spring Yingchun Liu, W. Kimryn Rathmell, Bizhan Bandarchi-Chamkhaleh, Wendy Winckler, David Mallery, Nicholas J. Petrelli, Nicole Todaro, Alex E. Lash, James Shin, Travis Brown, Igor Jurisica, Benjamin Gross, Hailei Zhang, Nikolaus Schultz, Kenna R. Mills Shaw, Nam Pho, William Pao, Darlene Lee, Zhen Fan, Troy Shelton, Yan Shi, Shelley Alonso, Carmelo Gaudioso, Peter B. Illei, Stuart R. Jefferys, Maureen F. Zakowski, Marian Rutledge, Bruce E. Johnson, Andrew J. Mungall, Eric S. Lander, Matthew G. Soloway, Michael Mayo, Christopher G. Maher, John V. Heymach, Lihua Zou, Dominique L. Berton, Nina Thiessen, Gary K. Scott, Anna L. Chu, Richard A. Hajek, Ming-Sound Tsao, Liming Yang, Qianxing Mo, Nguyen Van Bang, Martin Hirst, John Eckman, Erin Curley, Rajiv Dhir, Gad Getz, Stanley Girshik, Xuan Van Le, Jeff Boyd, Roman K. Thomas, Konstantin V. Fedosenko, Juok Cho, Alexei Protopopov, Nguyen Viet Tien, Lixing Yang, Laetitia Borsu, Steven J.M. Jones, Matthew D. Wilkerson, Mark Sherman, Andrew Crenshaw, Doug Voet, Elizabeth Buda, Jennifer Brown, Yaron S.N. Butterfield, Rehan Akbani, Todd Pihl, Ruibin Xi, Nianxiang Zhang, Jessica Walton, Ricardo Ramirez, Lisle E. Mose, Leslie Cope, Greg Eley, Mark A. Jensen, John N. Weinstein, Li Ding, Li-Wei Chang, Matthew C. Nicholls, Peter J. Park, Bui Duc Phu, Christopher R. Cabanski, Bernard Kohl, Julien Baboud, Joseph Paulauskis, David Pot, Gordon Robertson, Jingchun Zhu, John A. Demchok, Eunjung Lee, Giovanni Ciriello, Mary Iacocca, Gordon Saksena, Jesse Walsh, Yupu Liang, William K. Funkhouser, Rashmi N. Sanbhadti, Sam Ng, Venkatraman E. Seshan, Valerie W. Rusch, Robert A. Holt, Robert Sfeir, Jung E. Hye-Chun, Kai Wang, Helga Thorvaldsdottir, Huy V. Nguyen, Christopher Wilks, Brian Craft, Donghui Tan, David Haussler, Charles M. Perou, Timothy J. Triche, Christopher C. Benz, Scot Waring, Peggy Yena, Richard A. Moore, Darshan Singh, Andrew D. Cherniack, Rameen Beroukhim, Michael S. Lawrence, Xiaojia Ren, Stacey Gabriel, Martha Hatfield, Christine Czerwinski, Alan P. Hoyle, Marc Ladanyi, Joshua M. Stuart, Andrey Sivachenko, Jacqueline D. Palchik, Thomas Zeng, Inanc Birol, Rohini Raman, Ijeoma Azodo, Jianhua Zhang, Adam B. Olshen, Bradley A. Ozenberger, Angela Hadjipanayis, Sachet A. Shukla, Barry S. Taylor, John M. Greene, Jill P. Mesirov, Petar Stojanov, Raju Kucherlapati, Richard Corbett, Farhad Kosari, Martin L. Ferguson, Natasha Rekhtman, Keith A. Baggerly, Scott Morris, Brenda Rabeno, Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., and Park, Peter J.
Subjects: Lung Neoplasms, Squamous Differentiation, DNA Mutational Analysis, Adenocarcinoma of Lung, Biology, Adenocarcinoma, Article, Phosphatidylinositol 3-Kinases, Gefitinib, Mutation Rate, CDKN2A, Carcinoma, medicine, Humans, Molecular Targeted Therapy, Lung cancer, Multidisciplinary, Genome, Human, Gene Expression Profiling, Genes, p16, Genomics, medicine.disease, Genes, p53, Gene expression profiling, Gene Expression Regulation, Neoplastic, Mutation, Cancer research, Carcinoma, Squamous Cell, Gene Deletion, medicine.drug, Necitumumab, Signal Transduction
Abstract: Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers., National Institutes of Health (U.S.) (Grant U24 CA126561), National Institutes of Health (U.S.) (Grant U24 CA126551), National Institutes of Health (U.S.) (Grant U24 CA126554), National Institutes of Health (U.S.) (Grant U24 CA126543), National Institutes of Health (U.S.) (Grant U24 CA126546), National Institutes of Health (U.S.) (Grant U24 CA126563), National Institutes of Health (U.S.) (Grant U24 CA126544), National Institutes of Health (U.S.) (Grant U24 CA143845), National Institutes of Health (U.S.) (Grant U24 CA143858), National Institutes of Health (U.S.) (Grant U24 CA144025), National Institutes of Health (U.S.) (Grant U24 CA143882), National Institutes of Health (U.S.) (Grant U24 CA143866), National Institutes of Health (U.S.) (Grant U24 CA143867), National Institutes of Health (U.S.) (Grant U24 CA143848), National Institutes of Health (U.S.) (Grant U24 CA143840), National Institutes of Health (U.S.) (Grant U24 CA143835), National Institutes of Health (U.S.) (Grant U24 CA143799), National Institutes of Health (U.S.) (Grant U24 CA143883), National Institutes of Health (U.S.) (Grant U24 CA143843), National Institutes of Health (U.S.) (Grant U54 HG003067), National Institutes of Health (U.S.) (Grant U54 HG003079), National Institutes of Health (U.S.) (Grant U54 HG003273)
Published: 2012

16. Comprehensive molecular characterization of human colon and rectal cancer

Author: Donghui Tan, Nils Gehlenborg, Robert S. Fulton, Pat Swanson, Pei Lin, Chang-Jiun Wu, Piotr A. Mieczkowski, David Haussler, Marco A. Marra, Stephen E. Schumacher, Bernard Kohl, Jingchun Zhu, Lucinda Fulton, Charles M. Perou, Timothy J. Triche, Madhumati Gundapuneni, Mark Backus, Eve Shinbrot, Yonghong Xiao, Xuan Van Le, Liming Yang, Gad Getz, Stanley Girshik, Jessica Walton, Barbara Tabak, Greg Eley, Brian O'Connor, Larissa K. Temple, Saianand Balu, Eric A. Collisson, Tanja Davidsen, Elizabeth Buda, Janae V. Simons, Anisha Gulabani, Joseph Willis, Tod D. Casasent, Scott Morris, Doug Voat, Jireh Santibanez, Jennifer Drummond, Li Ding, Nicholas J. Petrelli, Andrew J. Mungall, Michael Mayo, Aaron D. Black, Gerald C. Chu, Elizabeth N. Medina, Huy V. Nguyen, Aaron E. Cozen, Yongjun Zhao, Hui Shen, Christopher Szeto, Brenda Rabeno, Martin Hirst, Bogumil Kaczkowski, Lisle E. Mose, Lora Lewis, Brian Craft, Joseph Paulauskis, Ari B. Kahn, Andy Chu, Peter W. Laird, Benjamin Gross, Matthew D. Wilkerson, Raju Kucherlapati, Matthew C. Nicholls, David Van Den Berg, Vesteinn Thorsson, Richard W. Park, Ethan Cerami, David A. Wheeler, Laura A.L. Dillon, Angela Tam, Julien Baboud, Kim D. Delehaunty, Katherine A. Hoadley, Ranabir Guin, Donna M. Muzny, Gordon Saksena, Shaowu Meng, Richard Kreisberg, Kenneth H. Buetow, Rajiv Dhir, Inanc Birol, Timo Erkkilä, Martin L. Ferguson, Robert A. Holt, Elaine R. Mardis, Aaron McKenna, Rohini Raman, Robert Sfeir, Mark Sherman, Andrew Crenshaw, J. Zachary Sanborn, Spring Yingchun Liu, Yuan Qing Wu, Jane Peterson, Eric E. Snyder, Lisa Iype, John N. Weinstein, Helga Thorvaldsdottir, Adam J. Bass, Dominik Stoll, Brady Bernard, Steven J.M. Jones, Peter Dolina, Julie M. Gastier-Foster, Jared R. Slobodan, Mark A. Jensen, Jacqueline E. Schein, Christie Kovar, Anders Jacobsen, Stephen C. Benz, J. Todd Auman, Juinhua Zhang, Peter Fielding, Paul T. Spellman, Jacqueline D. Palchik, Jay Bowen, Thomas Zeng, Douglas Voet, Arnulf Dörner, Joshua M. Stuart, Ryan Demeter, Theodore C. Goldstein, Keith A. Baggerly, Jorma J. de Ronde, Deepak Srinivasan, Boris Reva, Robert E. Pyatt, Andrew Kaufman, Timothy A. Chan, Alexei Protopopov, William G. Richards, Daniel R. Zerbino, Brenda Ayala, Martin R. Weiser, Psalm Haseley, Margaret Morgan, Mary Iacocca, Thomas Robinson, Chad J. Creighton, Dominique L. Berton, Da Yang, Peng Chieh Chen, Carl F. Schaefer, Peter White, Fred Denstman, Giovanni Ciriello, Matthew N. Bainbridge, Heidi J. Sofia, Irene Newsham, Jill P. Mesirov, Ling Li, Benjamin P. Berman, Daniel J. Weisenberger, Garrett M. Nash, Jason Walker, Nina Thiessen, Narayanan Sathiamoorthy, James A. Robinson, Petar Stojanov, Todd Wylie, Derek Y. Chiang, Kristin G. Ardlie, Jianjiong Gao, Lisa Wise, Bradley A. Ozenberger, Jeffrey G. Reid, Angela Hadjipanayis, Sachet A. Shukla, Barry S. Taylor, John M. Greene, Eric Chuah, Richard Varhol, Lisa R. Trevino, Charles J. Vaske, Ying Du, Arthur P. Goldberg, Rui Jing, Jon Whitmore, Joan Pontius, Yevgeniy Antipin, Kyle Ellrott, Nilsa C. Ramirez, Tom Bodenheimer, Junyuan Wu, Lynda Chin, Scott L. Carter, Hailei Zhang, Ryan Bressler, Adam Norberg, Stacey Gabriel, Martha Hatfield, Jonathan G. Seidman, Corbin D. Jones, Huyen Dinh, D. Neil Hayes, Christine Czerwinski, Gerald R. Fowler, Mark S. Guyer, Robert Penny, Alan P. Hoyle, Hartmut Juhl, Catrina Fronick, Margi Sheth, Christopher C. Benz, Scot Waring, Peggy Yena, Richard A. Moore, Darshan Singh, Toshinori Hinoue, Yaron S.N. Butterfield, Andrew D. Cherniack, Maria C. Mariano, Rameen Beroukhim, Michael S. Lawrence, Xiaojia Ren, Marc Ladanyi, Anna K. Unruh, Noreen Dhalla, Candace Shelton, Gary Witkin, Andrey Sivachenko, David Pot, Michael J. Zinner, Richard Thorp, Jan F. Prins, Eunjung Lee, A. Gordon Robertson, Wendy Winckler, Efsevia Vakiani, Chris Wakefield, Alex H. Ramos, Semin Lee, Zhining Wang, Sam Ng, Lihua Zhou, Christina Liquori, Rileen Sinha, Dennis T. Maglinte, Michael S. Noble, Haiyan I. Li, B. Arman Aksoy, Preethi H. Gunaratne, Michael Meyers, Daniel C. Koboldt, Lawrence A. Donehower, Darlene Lee, Jake Lin, Gary K. Scott, Hye Jung E. Chun, Sheila Reynolds, Anna L. Chu, Rehan Akbani, Todd Pihl, Ruibin Xi, Charles S. Fuchs, Nianxiang Zhang, Stanley R. Hamilton, Bradley M. Broom, Wei Zhang, Chris Sander, Marc Danie Nazaire, Carrie Hirst, Stephen B. Baylin, Joel E. Tepper, Kyle Chang, Miruna Balasundaram, Jen Brown, Yan Shi, Matthew G. Soloway, Richard A. Gibbs, Richard K. Wilson, Peter J. Park, Zhaoshi Zeng, John A. Demchok, Jesse Walsh, Rashmi N. Sanbhadti, Troy Shelton, Lixing Yang, Prachi Kothiyal, Monica M. Bertagnolli, Sean P. Barletta, Kristian Cibulskis, Yidi J. Turman, Nikolaus Schultz, Min Wang, Shelley Alonso, Carsten Zornig, P. Paty, Elizabeth J. Thomson, Peter A. Kigonya, Fei Pan, Yuexin Liu, Matthew Meyerson, Kenna R. Mills Shaw, Nam Pho, Stuart R. Jefferys, Daniel DiCara, Robert C. Onofrio, Erin Pleasance, Eric S. Lander, David J. Dooling, Christina Yau, Michael D. Topal, David B. Solit, Christopher Wilks, Ilya Shmulevich, Robin J.N. Coope, Ronglai Shen, Jose G. Guillem, R. Craig Cason, Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.
Subjects: DNA Copy Number Variations, Colorectal cancer, Biology, medicine.disease_cause, MLH1, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Mutation Rate, microRNA, medicine, Humans, Exome, 030304 developmental biology, 0303 health sciences, Multidisciplinary, POLD1, Rectal Neoplasms, Gene Expression Profiling, Microsatellite instability, Sequence Analysis, DNA, DNA Methylation, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, DNA methylation, Colonic Neoplasms, Mutation, Cancer research, KRAS
Abstract: To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ε (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression., National Institutes of Health (U.S.) (Grant U24CA143799), National Institutes of Health (U.S.) (Grant U24CA143835), National Institutes of Health (U.S.) (Grant U24CA143840), National Institutes of Health (U.S.) (Grant U24CA143843), National Institutes of Health (U.S.) (Grant U24CA143845), National Institutes of Health (U.S.) (Grant U24CA143848), National Institutes of Health (U.S.) (Grant U24CA143858), National Institutes of Health (U.S.) (Grant U24CA143866), National Institutes of Health (U.S.) (Grant U24CA143867), National Institutes of Health (U.S.) (Grant U24CA143882), National Institutes of Health (U.S.) (Grant U24CA143883), National Institutes of Health (U.S.) (Grant U24CA144025), National Institutes of Health (U.S.) (Grant U54HG003067), National Institutes of Health (U.S.) (Grant U54HG003079), National Institutes of Health (U.S.) (Grant U54HG003273)
Published: 2011

17. Integrated Genomic Characterization of Papillary Thyroid Carcinoma

Author: Piotr A. Mieczkowski, Nishant Agrawal, Yiling Lu, Junyuan Wu, Marco A. Marra, Fabio Vandin, Margi Sheth, Roy Tarnuzzer, Jacqueline E. Schein, Heidi J. Sofia, Lori Boice, Phillip H. Lai, Rajiv Dhir, Matthew D. Wilkerson, Benjamin Gross, Liming Yang, Pei Lin, Yaron S.N. Butterfield, Julie M. Gastier-Foster, Jiashan Zhang, Tanja Davidsen, Andy Chu, J. Todd Auman, Sheila Fisher, Harindra Arachchi, Andrew J. Mungall, Suresh Ramalingam, Rehan Akbani, Gad Getz, Ranabir Guin, Jianhua Zhang, Saianand Balu, A. Gordon Robertson, Michael Parfenov, Stuart R. Jefferys, Gordon Saksena, John Paul Shen, Richard A. Moore, Martha A. Zeiger, Adel K El-Naggar, Umadevi Veluvolu, Scott L. Carter, Ludmila Danilova, Scott Frazer, Tom Bodenheimer, Rebecca Carlsen, Tobias Carling, Robert A. Holt, Katayoon Kasaian, Matthew Rosenthal, Trey Ideker, Gabriel Sica, Jiabin Tang, Richard Kreisberg, Angela Hadjipanayis, Thomas J. Giordano, Esther Rheinbay, Greg Eley, Bradley A. Ozenberger, Karen Gomez-Hernandez, Jonathan G. Seidman, Corbin D. Jones, Michael L. Miller, Paul M. Weinberger, Matthew D. Ringel, James A. Fagin, Jean C. Zenklusen, Wei Zhang, Chandra Sekhar Pedamallu, Michael Mayo, Eunjung Lee, Donghui Tan, Evan O. Paull, Franklin W. Huang, Semin Lee, Shaowu Meng, Justin A. Bishop, Lixing Yang, Payal Sipahimalani, Kristen M. Leraas, Marc Ladanyi, Aaron D. Black, Carolyn M. Hutter, D. Neil Hayes, Charles M. Perou, Lisa Iype, Robert C. Smallridge, Amanda Clarke, Jonathan V. Eldridge, Raja R. Seethala, Jessica Frick, John N. Weinstein, B. Arman Aksoy, Sara Sadeghi, Moiz S. Bootwalla, Sheliann S. Dookran, Dong Zeng, Rileen Sinha, Yichao Sun, Adrian Ally, Hollie A. Harper, Barry S. Taylor, Sylvia L. Asa, Joel S. Parker, Jay Bowen, John A. Copland, Reanne Bowlby, Stephanie Eng, Jeffrey Roach, Kyle R. Covington, William Lee, David A. Wheeler, Nina Thiessen, Ronglai Shen, Yingchun Liu, Christopher B. Umbricht, David Van Den Berg, Katherine A. Hoadley, S. Onur Sumer, James G. Herman, Peter W. Laird, Harshad S. Mahadeshwar, Alexei Protopopov, Roeland Verhaak, Chip Stewart, Brady Bernard, Timothy R. Fennell, Timothy A. Chan, Steven I. Sherman, Ni Zhao, Sheila Reynolds, Ilya Shmulevich, Kristian Cibulskis, Ian Ganly, Erik Zmuda, Janae V. Simons, Taofeek K. Owonikoko, Nils Gehlenborg, Madhusmita Behera, Fadlo R. Khuri, Elizabeth Buda, Jinze Liu, Scot Waring, Darlene Lee, Yussanne Ma, Chris Sander, Shiyun Ling, Tara M. Lichtenberg, Yuri E. Nikiforov, Michelle D. Williams, Giovanni Ciriello, Robert L. Ferris, David G. McFadden, Petar Stojanov, Steven E. Schumacher, Raju Kucherlapati, Electron Kebebew, Daniel J. Weisenberger, Lynda Chin, Bradley A. Murray, Roger Kramer, Dorothy Cheung, Lee Lichtenstein, Akinyemi I. Ojesina, Anders Jacobsen, Mei Huang, Juok Cho, Robin Brookens, Michelle Vinco, Noreen Dhalla, Netty Santoso, Nils Weinhold, Angela Tam, Joshua M. Stuart, Jonna Grimsby, Kenna R. Mills Shaw, Doug Voet, Ricardo Ramirez, W. Kimryn Rathmell, Jianjiong Gao, Lisa Wise, Hailei Zhang, Eric S. Lander, Vesteinn Thorsson, Steven J.M. Jones, Liu Xi, Xingzhi Song, Matan Hofree, Gordon B. Mills, Matthew Meyerson, Nikolaus Schultz, Travis I. Zack, Lihua Zou, Leigh B. Thorne, Robert Bryant, Vonn Walter, Daniel DiCara, David J. Kwiatkowski, Benjamin J. Raphael, Stephen B. Baylin, Yan Shi, Matthew G. Soloway, Daniel A. Winer, Angeliki Pantazi, Gary L. Clayman, Sahil Seth, R. Michael Tuttle, Peter J. Park, Denise Brooks, John A. Demchok, Amy Chen, Jan F. Prins, Zhining Wang, Miruna Balasundaram, Michael S. Noble, Gideon Dresdner, Levi A. Garraway, Eric Chuah, Michael Rivera, Jaegil Kim, Mara Rosenberg, Barbara Tabak, David I. Heiman, Andrew D. Cherniack, Rameen Beroukhim, Michael S. Lawrence, Wen-Bin Liu, Carrie Sougnez, Xiaojia Ren, Ronald Ghossein, Richard A. Gibbs, Jocelyn Wilson, Stacey Gabriel, Samantha Sharpe, Virginia A. LiVolsi, Lisle E. Mose, Leslie Cope, Sally E. Carty, Nilsa C. Ramirez, Yasin Senbabaoglu, Christopher A. Bristow, Alan P. Hoyle, and Andrew Wei Xu
Subjects: Genetics and Molecular Biology (all), DNA Copy Number Variations, endocrine system diseases, Carcinoma, Gene Fusion, Humans, Thyroid Gland, Thyroid Neoplasms, Mutation, Biochemistry, Genetics and Molecular Biology (all), Medicine (all), Noninvasive follicular thyroid neoplasm with papillary-like nuclear features, EIF1AX, Biology, Bioinformatics, Biochemistry, Article, General Biochemistry, Genetics and Molecular Biology, Thyroid carcinoma, Poorly Differentiated Thyroid Carcinoma, medicine, CHEK2, Thyroid cancer, Biochemistry, Genetics and Molecular Biology(all), Thyroid, medicine.disease, Carcinoma, Papillary, Carcinoma/genetics, 3. Good health, medicine.anatomical_structure, Thyroid Cancer, Papillary, Thyroid Neoplasms/genetics, Thyroid Gland/cytology
Abstract: Summary Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX , PPM1D , and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF -mutant tumors, and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease.
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17 results on '"Daniel DiCara"'

1. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas

2. Comprehensive genomic characterization of head and neck squamous cell carcinomas

3. The Somatic Genomic Landscape of Glioblastoma

4. Mutational heterogeneity in cancer and the search for new cancer genes

5. COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

6. Integrated genomic characterization of endometrial carcinoma

7. A Landscape of Driver Mutations in Melanoma

8. Genomic Classification of Cutaneous Melanoma

9. Characterization of HPV and host genome interactions in primary head and neck cancers

10. The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

11. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

12. The Cancer Genome Atlas Pan-Cancer analysis project

13. Comprehensive molecular characterization of urothelial bladder carcinoma

14. Comprehensive molecular profiling of lung adenocarcinoma

15. Comprehensive genomic characterization of squamous cell lung cancers

16. Comprehensive molecular characterization of human colon and rectal cancer

17. Integrated Genomic Characterization of Papillary Thyroid Carcinoma

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17 results on '"Daniel DiCara"'

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