Integrated Genomic Characterization of Papillary Thyroid Carcinoma

All 324 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, Rameen Beroukhim, Bishop Ja, 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, Elizabeth Buda, Yaron S N. Butterfield, Tobias Carling, Rebecca Carlsen, Carter Sl, 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, Amanda Clarke, Clayman Gl, Gary L Clayman, Leslie Cope, Copland Ja, John A Copland, Kyle Covington, Ludmila Danilova, Tanja Davidsen, Demchok Ja, John A Demchok, Daniel DiCara, Noreen Dhalla, Rajiv Dhir, Sheliann Sheliann S Dookran, Gideon Dresdner, Jonathan Eldridge, El Naggar Ak, Greg Eley, Adel K El-Naggar, James A. Fagin, Stephanie Eng, Ferris Rl, Timothy Fennell, Robert L Ferris, Sheila Fisher, Scott Frazer, Gabriel Sb, Jessica Frick, Stacey B Gabriel, Ian Ganly, Garraway La, Jianjiong Gao, Levi A Garraway, Gastier Foster Jm, Julie M Gastier-Foster, Gad Getz, Nils Gehlenborg, Gibbs Ra, Ronald Ghossein, Richard A Gibbs, Giordano Tj, Thomas J Giordano, Karen Gomez-Hernandez, Jonna Grimsby, Benjamin Gross, Ranabir Guin, Harper Ha, Angela Hadjipanayis, Hollie A Harper, Heiman Di, D. Neil Neil Hayes, David I Heiman, Herman Jg, Katherine A. Hoadley, James G Herman, Matan Hofree, Holt Ra, Robert A Holt, Hoyle Ap, Alan P Hoyle, Huang Fw, Franklin W Huang, Mei Huang, Hutter Cm, Carolyn M Hutter, Trey Ideker, Lisa Iype, Anders Jacobsen, Jefferys Sr, Stuart R Jefferys, Jones Cd, Corbin D Jones, Steven J M. Jones, Katayoon Kasaian, Electron Kebebew, Khuri Fr, Fadlo R Khuri, Jaegil Kim, Roger Kramer, Richard Kreisberg, Raju Kucherlapati, Kwiatkowski Dj, David J Kwiatkowski, Phillip H. Lai, Marc Ladanyi, Laird Pw, Peter W Laird, Eric Lander, Lawrence Ms, Michael S Lawrence, Darlene Lee, Eunjung Lee, Semin Lee, William Lee, Leraas Km, Kristen M Leraas, Lichtenberg Tm, Tara M Lichtenberg, Lee Lichtenstein, Pei Lin, Shiyun Ling, Jinze Liu, Wenbin Liu, Yingchun Liu, LiVolsi Va, Virginia A LiVolsi, Yiling Lu, Yussanne, Yussanne Ma, Mahadeshwar Hs, Harshad S Mahadeshwar, Marco A. Marra, Michael Mayo, McFadden Dg, David G McFadden, Shaowu Meng, Matthew Meyerson, Mieczkowski Pa, Piotr A Mieczkowski, Michael Miller, Gordon Mills, Moore Ra, 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, Ozenberger Ba, Michael Parfenov, Peter J Park, Joel S Parker, Park Pj, Evan O Paull, Parker Js, Chandra Sekhar Pedamallu, Paull Eo, Charles M Perou, Pedamallu Cs, Jan F Prins, Perou Cm, Alexei Protopopov, Suresh Suresh S Ramalingam, Prins Jf, Nilsa C Ramirez, Ricardo Ramirez, Benjamin J Raphael, Ramirez Nc, W. Kimryn Kimryn Rathmell, Xiaojia Ren, Raphael Bj, Sheila M Reynolds, Esther Rheinbay, Matthew D Ringel, Reynolds Sm, Michael Rivera, Jeffrey Roach, Ringel Md, A. Gordon Gordon Robertson, Mara W Rosenberg, Matthew Rosenthal, Sara Sadeghi, Rosenberg Mw, Gordon Saksena, Chris Sander, Netty Santoso, Jacqueline E Schein, Nikolaus Schultz, Steven E Schumacher, Schein Je, Raja Raja R Seethala, Jonathan Seidman, Schumacher Se, Yasin Senbabaoglu, Sahil Seth, Samantha Sharpe, John P Shen, Kenna R. Mills Shaw, Ronglai Shen, Shen Jp, Steven Sherman, Margi Sheth, Yan Shi, Ilya Shmulevich, Gabriel L Sica, Sica Gl, Janae Simons, Rileen Sinha, Simons Jv, Payal Sipahimalani, Robert C Smallridge, Heidi J Sofia, Smallridge Rc, Matthew G Soloway, Sofia Hj, Xingzhi Song, Carrie Sougnez, Soloway Mg, Chip Stewart, Petar Stojanov, Joshua M Stuart, S. Onur Onur Sumer, Yichao Sun, Stuart Jm, Barbara Tabak, Angela Tam, Donghui Tan, Jiabin Tang, Roy Tarnuzzer, Barry S Taylor, Nina Thiessen, Taylor Bs, Leigh Thorne, Vésteinn Thorsson, R. Michael Michael Tuttle, Christopher B Umbricht, David J Van Den Berg, Umbricht Cb, Fabio Vandin, Van Den Berg Dj, Umadevi Veluvolu, 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.