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 Bowlby; Christopher 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

doi:10.1016/j.cell.2014.09.050

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

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

2359 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 language	English (US)
Pages (from-to)	676-690
Number of pages	15
Journal	Cell
Volume	159
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2014.09.050
State	Published - Oct 23 2014

Funding

We are grateful to all the patients and families who contributed to this study, to Chris Gunter for editing, and Margi Sheth and Jiashan (Julia) Zhang for project management. Thomas Giordano thanks his colleagues who covered his clinical duties. Supported by the following grants from the United States National Institutes of Health: 5U24CA143799, 5U24CA143835, 5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA143858, 5U24CA143866, 5U24CA143867, 5U24CA143882, 5U24CA143883, 5U24CA144025, U54HG003067, U54HG003079, and U54HG003273, P30CA16672. Yuri Nikiforov is a consultant for Quest Diagnostics. Raju Kucherlapati serves on the Board of Directors of KEW Group, Inc. Daniel J. Weisenberger is a consultant for Zymo Research Corporation.

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cell.2014.09.050

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

@article{aa6084b5fe7f4fd29f6bb0628fc65eaf,

title = "Integrated Genomic Characterization of Papillary Thyroid Carcinoma",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2014 The Authors.",

year = "2014",

month = oct,

day = "23",

doi = "10.1016/j.cell.2014.09.050",

language = "English (US)",

volume = "159",

pages = "676--690",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "3",

}

Agrawal, N, Akbani, R, Aksoy, BA, Ally, A, Arachchi, H, Asa, SL, Auman, JT, Balasundaram, M, Balu, S, Baylin, SB, Behera, M, Bernard, B, Beroukhim, R, Bishop, JA, Black, AD, Bodenheimer, T, Boice, L, Bootwalla, MS, Bowen, J, Bowlby, R, Bristow, CA, Brookens, R, Brooks, D, Bryant, R, Buda, E, Butterfield, YSN, Carling, T, Carlsen, R, Carter, SL, Carty, SE, Chan, TA, Chen, AY, Cherniack, AD, Cheung, D, Chin, L, Cho, J, Chu, A, Chuah, E, Cibulskis, K, Ciriello, G, Clarke, A, Clayman, GL, Cope, L, Copland, JA, Covington, K, Danilova, L, Davidsen, T, Demchok, JA, DiCara, D, Dhalla, N, Dhir, R, Dookran, SS, Dresdner, G, Eldridge, J, Eley, G, El-Naggar, AK, Eng, S, Fagin, JA, Fennell, T, Ferris, RL, Fisher, S, Frazer, S, Frick, J, Gabriel, SB, Ganly, I, Gao, J, Garraway, LA, Gastier-Foster, JM, Getz, G, Gehlenborg, N, Ghossein, R, Gibbs, RA, Giordano, TJ, Gomez-Hernandez, K, Grimsby, J, Gross, B, Guin, R, Hadjipanayis, A, Harper, HA, Hayes, DN, Heiman, DI, Herman, JG, Hoadley, KA, Hofree, M, Holt, RA, Hoyle, AP, Huang, FW, Huang, M, Hutter, CM, Ideker, T, Iype, L, Jacobsen, A, Jefferys, SR, Jones, CD, Jones, SJM, Kasaian, K, Kebebew, E, Khuri, FR, Kim, J, Kramer, R, Kreisberg, R, Kucherlapati, R, Kwiatkowski, DJ, Ladanyi, M, Lai, PH, Laird, PW, Lander, E, Lawrence, MS, Lee, D, Lee, E, Lee, S, Lee, W, Leraas, KM, Lichtenberg, TM, Lichtenstein, L, Lin, P, Ling, S, Liu, J, Liu, W, Liu, Y, LiVolsi, VA, Lu, Y, Ma, Y, Mahadeshwar, HS, Marra, MA, Mayo, M, McFadden, DG, Meng, S, Meyerson, M, Mieczkowski, PA, Miller, M, Mills, G, Moore, RA, Mose, LE, Mungall, AJ, Murray, BA, Nikiforov, YE, Noble, MS, Ojesina, AI, Owonikoko, TK, Ozenberger, BA, Pantazi, A, Parfenov, M, Park, PJ, Parker, JS, Paull, EO, Pedamallu, CS, Perou, CM, Prins, JF, Protopopov, A, Ramalingam, SS, Ramirez, NC, Ramirez, R, Raphael, BJ, Rathmell, WK, Ren, X, Reynolds, SM, Rheinbay, E, Ringel, MD, Rivera, M, Roach, J, Robertson, AG, Rosenberg, MW, Rosenthal, M, Sadeghi, S, Saksena, G, Sander, C, Santoso, N, Schein, JE, Schultz, N, Schumacher, SE, Seethala, RR, Seidman, J, Senbabaoglu, Y, Seth, S, Sharpe, S, Shaw, KRM, Shen, JP, Shen, R, Sherman, S, Sheth, M, Shi, Y, Shmulevich, I, Sica, GL, Simons, JV, Sinha, R, Sipahimalani, P, Smallridge, RC, Sofia, HJ, Soloway, MG, Song, X, Sougnez, C, Stewart, C, Stojanov, P, Stuart, JM, Sumer, SO, Sun, Y, Tabak, B, Tam, A, Tan, D, Tang, J, Tarnuzzer, R, Taylor, BS, Thiessen, N, Thorne, L, Thorsson, V, Tuttle, RM, Umbricht, CB, Van Den Berg, DJ, Vandin, F, Veluvolu, U, Verhaak, RGW, Vinco, M, Voet, D, Walter, V, Wang, Z, Waring, S, Weinberger, PM, Weinhold, N, Weinstein, JN, Weisenberger, DJ, Wheeler, D, Wilkerson, MD, Wilson, J, Williams, M, Winer, DA, Wise, L, Wu, J, Xi, L, Xu, AW, Yang, L, Yang, L, Zack, TI, Zeiger, MA, Zeng, D, Zenklusen, JC, Zhao, N, Zhang, H, Zhang, J, Zhang, J, Zhang, W, Zmuda, E & Zou, L 2014, 'Integrated Genomic Characterization of Papillary Thyroid Carcinoma', Cell, vol. 159, no. 3, pp. 676-690. https://doi.org/10.1016/j.cell.2014.09.050

TY - JOUR

T1 - Integrated Genomic Characterization of Papillary Thyroid Carcinoma

AU - Agrawal, Nishant

AU - Akbani, Rehan

AU - Aksoy, B. Arman

AU - Ally, Adrian

AU - Arachchi, Harindra

AU - Asa, Sylvia L.

AU - Auman, J. Todd

AU - Balasundaram, Miruna

AU - Balu, Saianand

AU - Baylin, Stephen B.

AU - Behera, Madhusmita

AU - Bernard, Brady

AU - Beroukhim, Rameen

AU - Bishop, Justin A.

AU - Black, Aaron D.

AU - Bodenheimer, Tom

AU - Boice, Lori

AU - Bootwalla, Moiz S.

AU - Bowen, Jay

AU - Bowlby, Reanne

AU - Bristow, Christopher A.

AU - Brookens, Robin

AU - Brooks, Denise

AU - Bryant, Robert

AU - Buda, Elizabeth

AU - Butterfield, Yaron S.N.

AU - Carling, Tobias

AU - Carlsen, Rebecca

AU - Carter, Scott L.

AU - Carty, Sally E.

AU - Chan, Timothy A.

AU - Chen, Amy Y.

AU - Cherniack, Andrew D.

AU - Cheung, Dorothy

AU - Chin, Lynda

AU - Cho, Juok

AU - Chu, Andy

AU - Chuah, Eric

AU - Cibulskis, Kristian

AU - Ciriello, Giovanni

AU - Clarke, Amanda

AU - Clayman, Gary L.

AU - Cope, Leslie

AU - Copland, John A.

AU - Covington, Kyle

AU - Danilova, Ludmila

AU - Davidsen, Tanja

AU - Demchok, John A.

AU - DiCara, Daniel

AU - Dhalla, Noreen

AU - Dhir, Rajiv

AU - Dookran, Sheliann S.

AU - Dresdner, Gideon

AU - Eldridge, Jonathan

AU - Eley, Greg

AU - El-Naggar, Adel K.

AU - Eng, Stephanie

AU - Fagin, James A.

AU - Fennell, Timothy

AU - Ferris, Robert L.

AU - Fisher, Sheila

AU - Frazer, Scott

AU - Frick, Jessica

AU - Gabriel, Stacey B.

AU - Ganly, Ian

AU - Gao, Jianjiong

AU - Garraway, Levi A.

AU - Gastier-Foster, Julie M.

AU - Getz, Gad

AU - Gehlenborg, Nils

AU - Ghossein, Ronald

AU - Gibbs, Richard A.

AU - Giordano, Thomas J.

AU - Gomez-Hernandez, Karen

AU - Grimsby, Jonna

AU - Gross, Benjamin

AU - Guin, Ranabir

AU - Hadjipanayis, Angela

AU - Harper, Hollie A.

AU - Hayes, D. Neil

AU - Heiman, David I.

AU - Herman, James G.

AU - Hoadley, Katherine A.

AU - Hofree, Matan

AU - Holt, Robert A.

AU - Hoyle, Alan P.

AU - Huang, Franklin W.

AU - Huang, Mei

AU - Hutter, Carolyn M.

AU - Ideker, Trey

AU - Iype, Lisa

AU - Jacobsen, Anders

AU - Jefferys, Stuart R.

AU - Jones, Corbin D.

AU - Jones, Steven J.M.

AU - Kasaian, Katayoon

AU - Kebebew, Electron

AU - Khuri, Fadlo R.

AU - Kim, Jaegil

AU - Kramer, Roger

AU - Kreisberg, Richard

AU - Kucherlapati, Raju

AU - Kwiatkowski, David J.

AU - Ladanyi, Marc

AU - Lai, Phillip H.

AU - Laird, Peter W.

AU - Lander, Eric

AU - Lawrence, Michael S.

AU - Lee, Darlene

AU - Lee, Eunjung

AU - Lee, Semin

AU - Lee, William

AU - Leraas, Kristen M.

AU - Lichtenberg, Tara M.

AU - Lichtenstein, Lee

AU - Lin, Pei

AU - Ling, Shiyun

AU - Liu, Jinze

AU - Liu, Wenbin

AU - Liu, Yingchun

AU - LiVolsi, Virginia A.

AU - Lu, Yiling

AU - Ma, Yussanne

AU - Mahadeshwar, Harshad S.

AU - Marra, Marco A.

AU - Mayo, Michael

AU - McFadden, David G.

AU - Meng, Shaowu

AU - Meyerson, Matthew

AU - Mieczkowski, Piotr A.

AU - Miller, Michael

AU - Mills, Gordon

AU - Moore, Richard A.

AU - Mose, Lisle E.

AU - Mungall, Andrew J.

AU - Murray, Bradley A.

AU - Nikiforov, Yuri E.

AU - Noble, Michael S.

AU - Ojesina, Akinyemi I.

AU - Owonikoko, Taofeek K.

AU - Ozenberger, Bradley A.

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AU - Prins, Jan F.

AU - Protopopov, Alexei

AU - Ramalingam, Suresh S.

AU - Ramirez, Nilsa C.

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AU - Raphael, Benjamin J.

AU - Rathmell, W. Kimryn

AU - Ren, Xiaojia

AU - Reynolds, Sheila M.

AU - Rheinbay, Esther

AU - Ringel, Matthew D.

AU - Rivera, Michael

AU - Roach, Jeffrey

AU - Robertson, A. Gordon

AU - Rosenberg, Mara W.

AU - Rosenthal, Matthew

AU - Sadeghi, Sara

AU - Saksena, Gordon

AU - Sander, Chris

AU - Santoso, Netty

AU - Schein, Jacqueline E.

AU - Schultz, Nikolaus

AU - Schumacher, Steven E.

AU - Seethala, Raja R.

AU - Seidman, Jonathan

AU - Senbabaoglu, Yasin

AU - Seth, Sahil

AU - Sharpe, Samantha

AU - Shaw, Kenna R.Mills

AU - Shen, John P.

AU - Shen, Ronglai

AU - Sherman, Steven

AU - Sheth, Margi

AU - Shi, Yan

AU - Shmulevich, Ilya

AU - Sica, Gabriel L.

AU - Simons, Janae V.

AU - Sinha, Rileen

AU - Sipahimalani, Payal

AU - Smallridge, Robert C.

AU - Sofia, Heidi J.

AU - Soloway, Matthew G.

AU - Song, Xingzhi

AU - Sougnez, Carrie

AU - Stewart, Chip

AU - Stojanov, Petar

AU - Stuart, Joshua M.

AU - Sumer, S. Onur

AU - Sun, Yichao

AU - Tabak, Barbara

AU - Tam, Angela

AU - Tan, Donghui

AU - Tang, Jiabin

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AU - Taylor, Barry S.

AU - Thiessen, Nina

AU - Thorne, Leigh

AU - Thorsson, Vésteinn

AU - Tuttle, R. Michael

AU - Umbricht, Christopher B.

AU - Van Den Berg, David J.

AU - Vandin, Fabio

AU - Veluvolu, Umadevi

AU - Verhaak, Roel G.W.

AU - Vinco, Michelle

AU - Voet, Doug

AU - Walter, Vonn

AU - Wang, Zhining

AU - Waring, Scot

AU - Weinberger, Paul M.

AU - Weinhold, Nils

AU - Weinstein, John N.

AU - Weisenberger, Daniel J.

AU - Wheeler, David

AU - Wilkerson, Matthew D.

AU - Wilson, Jocelyn

AU - Williams, Michelle

AU - Winer, Daniel A.

AU - Wise, Lisa

AU - Wu, Junyuan

AU - Xi, Liu

AU - Xu, Andrew W.

AU - Yang, Liming

AU - Yang, Lixing

AU - Zack, Travis I.

AU - Zeiger, Martha A.

AU - Zeng, Dong

AU - Zenklusen, Jean Claude

AU - Zhao, Ni

AU - Zhang, Hailei

AU - Zhang, Jianhua

AU - Zhang, Jiashan

AU - Zhang, Wei

AU - Zmuda, Erik

AU - Zou, Lihua

PY - 2014/10/23

Y1 - 2014/10/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84908335908&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908335908&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2014.09.050

DO - 10.1016/j.cell.2014.09.050

M3 - Article

C2 - 25417114

AN - SCOPUS:84908335908

SN - 0092-8674

VL - 159

SP - 676

EP - 690

JO - Cell

JF - Cell

IS - 3

ER -

Integrated Genomic Characterization of Papillary Thyroid Carcinoma

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