Integrated Genomic Characterization of Papillary Thyroid Carcinoma

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

*Corresponding author for this work

Research output: Contribution to journalArticle

1127 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)676-690
Number of pages15
JournalCell
Volume159
Issue number3
DOIs
StatePublished - Oct 23 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Agrawal, N., Akbani, R., Aksoy, B. A., Ally, A., Arachchi, H., Asa, S. L., Auman, J. T., Balasundaram, M., Balu, S., Baylin, S. B., Behera, M., Bernard, B., Beroukhim, R., Bishop, J. A., Black, A. D., Bodenheimer, T., Boice, L., Bootwalla, M. S., Bowen, J., ... Zou, L. (2014). Integrated Genomic Characterization of Papillary Thyroid Carcinoma. Cell, 159(3), 676-690. https://doi.org/10.1016/j.cell.2014.09.050