Integrated Genomic Characterization of Papillary Thyroid Carcinoma

All 328 authors (show less):
Nishant Agrawal, Rehan Akbani, B. Arman Arman Aksoy, Adrian Ally, Harindra Arachchi, Sylvia L Asa, Asa Sl, J. Todd Todd Auman, Miruna Balasundaram, Saianand Balu, Baylin Sb, Stephen B Baylin, Madhusmita Behera, Brady Bernard, Bishop Ja, Rameen Beroukhim, Justin A Bishop, Black Ad, Aaron D Black, Tom Bodenheimer, Lori Boice, Moiz S Bootwalla, Bootwalla Ms, Jay Bowen, Reanne Bowlby, Christopher A Bristow, Bristow Ca, Robin Brookens, Denise Brooks, Robert Bryant, Yaron S N. Butterfield, Elizabeth Buda, Tobias Carling, Yaron S N. Butterfield, Carter Sl, Rebecca Carlsen, Scott L Carter, Carty Se, Sally E Carty, Chan Ta, Timothy A Chan, Amy Y Chen, Chen Ay, Andrew D Cherniack, Cherniack Ad, Dorothy Cheung, Lynda Chin, Juok Cho, Andy Chu, Eric Chuah, Kristian Cibulskis, Giovanni Ciriello, Clayman Gl, Amanda Clarke, Gary L Clayman, Copland Ja, Leslie Cope, John A Copland, Kyle Covington, Ludmila Danilova, Demchok Ja, Tanja Davidsen, John A Demchok, Daniel DiCara, Noreen Dhalla, Rajiv Dhir, Sheliann Sheliann S Dookran, Gideon Dresdner, El Naggar Ak, Jonathan Eldridge, Adel K El-Naggar, Greg Eley, Ferris Rl, Stephanie Eng, James A. Fagin, Robert L Ferris, Timothy Fennell, Gabriel Sb, Sheila Fisher, Scott Frazer, Stacey B Gabriel, Jessica Frick, Garraway La, Ian Ganly, Levi A Garraway, Jianjiong Gao, Gastier Foster Jm, Julie M Gastier-Foster, Gad Getz, Gibbs Ra, Nils Gehlenborg, Richard A Gibbs, Ronald Ghossein, Giordano Tj, Thomas J Giordano, Karen Gomez-Hernandez, Jonna Grimsby, Harper Ha, Benjamin Gross, Ranabir Guin, Hollie A Harper, Angela Hadjipanayis, Heiman Di, David I Heiman, D. Neil Neil Hayes, Herman Jg, James G Herman, Katherine A. Hoadley, Holt Ra, Matan Hofree, Robert A Holt, Hoyle Ap, Alan P Hoyle, Huang Fw, Franklin W Huang, Hutter Cm, Mei Huang, Carolyn M Hutter, Trey Ideker, Lisa Iype, Jefferys Sr, Anders Jacobsen, Stuart R Jefferys, Jones Cd, Corbin D Jones, Steven J M. Jones, Steven J M. Jones, Katayoon Kasaian, Khuri Fr, Electron Kebebew, Fadlo R Khuri, Jaegil Kim, Roger Kramer, Richard Kreisberg, Kwiatkowski Dj, Raju Kucherlapati, David J Kwiatkowski, Marc Ladanyi, Phillip H. Lai, Laird Pw, Peter W Laird, Lawrence Ms, Eric Lander, Michael S Lawrence, Darlene Lee, Eunjung Lee, Semin Lee, Leraas Km, William Lee, Kristen M Leraas, Lichtenberg Tm, Tara M Lichtenberg, Lee Lichtenstein, Pei Lin, Shiyun Ling, Jinze Liu, Wenbin Liu, LiVolsi Va, Yingchun Liu, Virginia A LiVolsi, Yussanne, Yiling Lu, Mahadeshwar Hs, Yussanne Ma, Harshad S Mahadeshwar, Marco A. Marra, McFadden Dg, Michael Mayo, David G McFadden, Shaowu Meng, Mieczkowski Pa, Matthew Meyerson, Piotr A Mieczkowski, Michael Miller, Moore Ra, Gordon Mills, Richard A Moore, Mose Le, Lisle E Mose, Mungall Aj, Andrew J MungallORCID, Bradley A Murray, Murray Ba, Yuri E Nikiforov, Nikiforov Ye, Michael S Noble, Noble Ms, Akinyemi I Ojesina, Ojesina Ai, Taofeek K Owonikoko, Bradley A Ozenberger, Owonikoko Tk, Angeliki Pantazi, Michael Parfenov, Ozenberger Ba, Peter J Park, Joel S Parker, Park Pj, Evan O Paull, Parker Js, Chandra Sekhar Pedamallu, Paull Eo, Charles M Perou, Pedamallu Cs, Alexei Protopopov, Jan F Prins, Suresh Suresh S Ramalingam, Perou Cm, Ricardo Ramirez, Prins Jf, Nilsa C Ramirez, W. Kimryn Kimryn Rathmell, Benjamin J Raphael, Xiaojia Ren, Ramirez Nc, Esther Rheinbay, Raphael Bj, Sheila M Reynolds, Michael Rivera, Matthew D Ringel, Jeffrey Roach, Reynolds Sm, A. Gordon Gordon Robertson, Ringel Md, Matthew Rosenthal, Sara Sadeghi, Mara W Rosenberg, Gordon Saksena, Chris Sander, Rosenberg Mw, Netty Santoso, Nikolaus Schultz, Jacqueline E Schein, Raja Raja R Seethala, Steven E Schumacher, Jonathan Seidman, Schein Je, Yasin Senbabaoglu, Sahil Seth, Schumacher Se, Samantha Sharpe, Kenna R. Mills Shaw, John P Shen, Ronglai Shen, Steven Sherman, Shen Jp, Margi Sheth, Yan Shi, Ilya Shmulevich, Gabriel L Sica, Janae V. Simons, Sica Gl, Rileen Sinha, Payal Sipahimalani, Simons Jv, Robert C Smallridge, Heidi J Sofia, Smallridge Rc, Xingzhi Song, Matthew G Soloway, Sofia Hj, Carrie Sougnez, Chip Stewart, Petar Stojanov, Soloway Mg, S. Onur Onur Sumer, Joshua M Stuart, Yichao Sun, Barbara Tabak, Stuart Jm, Angela Tam, Donghui Tan, Jiabin Tang, Roy Tarnuzzer, Barry S Taylor, Nina Thiessen, Leigh Thorne, Taylor Bs, Vésteinn Thorsson, R. Michael Michael Tuttle, David J Van Den Berg, Christopher B Umbricht, David J Van Den Berg, Umbricht Cb, Fabio Vandin, Umadevi Veluvolu, Roel G W. Verhaak, Van Den Berg Dj, Roel G W. Verhaak, Michelle Vinco, Doug Voet, Vonn Walter, Zhining Wang, Scot Waring, Paul M Weinberger, Weinberger Pm, Nils Weinhold, John N Weinstein, Weinstein Jn, Daniel J Weisenberger, Weisenberger Dj, David Wheeler, Matthew D Wilkerson, Jocelyn Wilson, Wilkerson Md, Michelle Williams, Daniel A. Winer, Lisa Wise, Junyuan Wu, Liu Xi, Andrew W Xu, Xu Aw, Liming Yang, Lixing Yang, Zack Ti, Travis I Zack, Martha A. Zeiger, Dong Zeng, Zenklusen Jc, Jean Claude Zenklusen, Ni Zhao, Hailei Zhang, Jianhua Zhang, Zhang Jj, Jiashan (Julia) Zhang, Wei Zhang, Erik Zmuda, Lihua Zou

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Abstract
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.