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 | |
State | Published - Oct 23 2014 |
All Science Journal Classification (ASJC) codes
- General Biochemistry, Genetics and Molecular Biology
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In: Cell, Vol. 159, No. 3, 23.10.2014, p. 676-690.
Research output: Contribution to journal › Article › peer-review
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.
AU - Pantazi, Angeliki
AU - Parfenov, Michael
AU - Park, Peter J.
AU - Parker, Joel S.
AU - Paull, Evan O.
AU - Pedamallu, Chandra Sekhar
AU - Perou, Charles M.
AU - Prins, Jan F.
AU - Protopopov, Alexei
AU - Ramalingam, Suresh S.
AU - Ramirez, Nilsa C.
AU - Ramirez, Ricardo
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
AU - Tarnuzzer, Roy
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
N1 - Publisher Copyright: © 2014 The Authors.
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 -