Open AccessIntegrated Genomic Characterization of Papillary Thyroid Carcinoma
Author(s) -
Nishant Agrawal,
Rehan Akbani,
Bülent Arman Aksoy,
Adrian Ally,
Harindra Arachchi,
L. Sylvia,
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,
Arnoud Boot,
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 R. Covington,
Ludmila Danilova,
Tanja M. Davidsen,
John A. Demchok,
Daniel DiCara,
Noreen Dhalla,
Rajiv Dhir,
Sheliann S. Dookran,
Gideon Dresdner,
Jonathan Eldridge,
Greg Eley,
Adel K. ElNaggar,
Stephanie Eng,
James A. Fagin,
Timothy R. Fennell,
Robert L. Ferris,
Sheila Fisher,
Scott Frazer,
Jessica Frick,
Stacey 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 J. Skanderup,
Joshua M. Stuart,
Corbin D. Jones,
Steven J.M. Jones,
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 Alice Lee,
Semin Lee,
William Lee,
Kristen 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 B. 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 Paull,
Chandra Sekhar Pedamallu,
Charles M. Perou,
Jan F. Prins,
Alexei Protopopov,
Suresh S. Ramalingam,
Nilsa C. Ramirez,
Ricardo Ramírez,
Benjamin J. Raphael,
W. Kimryn Rathmell,
Xiaojia Ren,
Sheila M. Reynolds,
Esther Rheinbay,
Matthew D. Ringel,
Michael Rivera,
Jeffrey Roach,
A. Gordon Robertson,
Mara Rosenberg,
Matthew Rosenthal,
Sara Sadeghi,
Gordon Saksena,
Chris Sander,
Netty Santoso,
Jacqueline E. Schein,
Nikolaus Schultz,
Steven E. Schumacher,
Raja R. Seethala,
Jonathan G. Seidman,
Yasin Şenbabaoğlu,
Sahil Seth,
Samantha Sharpe,
Kenna Shaw,
John Paul Shen,
Ronglai Shen,
Steven I. Sherman,
Margi Sheth,
Yan Shi,
Ilya Shmulevich,
Gabriel 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,
S. Onur Sumer,
Yichao Sun,
Barbara Tabak,
Angela Tam,
Donghui Tan,
Jiabin Tang,
Roy Tarnuzzer,
Barry S. Taylor,
Nina Thiessen,
Leigh B. Thorne,
Vésteinn Thórsson,
R. Michael Tuttle,
Christopher B. Umbricht,
David Van Den Berg,
Fabio Vandin,
Umadevi Veluvolu,
Roel G.W. Verhaak,
Michelle Vinco,
Doug Voet,
Vonn Walter,
Linghua Wang,
Stephen C. Waring,
Paul Weinberger,
Nils Weinhold,
John N. Weinstein,
Daniel J. Weisenberger,
David A. Wheeler,
Matthew D. Wilkerson,
Jocelyn Wilson,
Michelle D. Williams,
Daniel A. Winer,
Lisa Wise,
Junyuan Wu,
Xi Liu,
Andrew Wei Xu,
Liming Yang,
Lixing Yang,
Travis Zack,
Martha A. Zeiger,
Dong Zeng,
Jean C. Zenklusen,
Ni Zhao,
Hailei Zhang,
Jianhua Zhang,
Jiashan Zhang,
Wei Zhang,
Erik Zmuda,
Lihua Zou
Publication year - 2014
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2014.09.050
Subject(s) - biology , thyroid carcinoma , cancer research , thyroid cancer , gene , mutation , carcinoma , cancer , thyroid , genetics , computational biology
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.
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