SUPPLEMENTAL AUTHOR INFORMATION

SUPPLEMENTAL AUTHOR INFORMATION

The Cancer Genome Atlas research network contributed collectively to this study. Biospecimens were provided by the Tissue Source Sites and processed by the Biospecimen Core Resource. Data generation and analyses were performed by the Genome-Sequencing Centers, Cancer Genome-Characterization Centers and Genome Data Analysis Centers. All data were released through the Data Coordinating Center. The NCI and NHGRI project teams coordinated project activities. We also acknowledge the following TCGA investigators of the Thyroid Analysis Working Group who contributed substantially to the project. Project leaders: G. Getz and T.J. Giordano. Analysis coordinator: C. Stewart. Data coordinator: J. Cho. Manuscript

coordinator: T.J. Giordano. Project coordinators: M. Sheth and J. Zhang. Clinical expertise and data analysis: S. L. Asa, J. Bowen, J.A. Fagin, I. Ganly, T.J. Giordano, E. Kebebew, L. Iype, K.M. Leraas, T. M. Lichtenberg, D.G. McFadden, A. Protopopov, M.D. Ringel, R. C. Smallridge, C.B. Umbricht, Y.E. Nikiforov and M.A. Zeiger. Supplemental pathology review: S.L. Asa, T.J. Giordano, R. Ghossein, Justin A. Bishop and Y.E. Nikiforov. DNA sequence and copy number analysis: A. D. Cherniack, J. Cho, G. Getz, K. Kasaian, J. Kim, D. J.

Kwiatkowski, L. Lichtenstein, B. A. Murray, E. Rheinbay, M. Rosenberg, G. Saksena, C.

Sougnez, and C. Stewart. TERT promoter sequencing and analysis: C. Stewart, C. Sougnez, J. Grimsby, F.W. Huang, L.A. Garraway, S.D. Doorkran, Y.E. Nikiforov, A. Hadjipanayis, R. Kucherlapati, G. Getz. Gene fusions: A. Hadjipanayis, K. A. Hoadley, R. Kucherlapati, C. Stewart and T.J. Giordano. Viral sequence detection: A.I. Ojesina, M. Meyerson. C. S. Pedamallu. S. Sadeghi, Y. Ma. DNA methylation analysis: L. Cope and L. Danilova. mRNA analysis: K. A. Hoadley, C. Stewart, V. Walter, N. Zhao and A. Hadjipanayis. miRNA analysis: L. Iype and A.G. Robertson. Pathway/Network/Integrated analysis: G. Ciriello, J.A. Fagin, N. Gehlenborg, M. Hofree, L. Iype, E.O. Paull, B.J. Raphael, M.D. Ringel, A.G. Robertson, J. Stuart, N. Schultz, Y. Senbabaoglu, and F. Vandin. Dark matter analysis: J. Cho, C. Stewart, and T.J. Giordano. Thyroid differentiation analysis: J. Kim, L. Danilova, L. Iype, A.G.

Robertson, C. Stewart, G. Getz, and T.J. Giordano. RPPA analysis: R. Akbani, W. Liu, and G. B. Mills. Supercluster: R. Akbani. Batch effects analysis: R. Akbani, S. Ling, and J. N. Weinstein. Manuscript review: M. Meyerson and R. Kucherlapati. Contact PIs: T.J. Giordano and G. Getz.

The Cancer Genome Atlas Research Network

Analysis working group: BC Cancer Agency, Katayoon Kasaian1, A. Gordon Robertson1, Brown University, Jonathan Eldridge2, Benjamin J. Raphael2, Fabio Vandin2, University of California San Diego, Matan Hofree3, Trey Ideker4, John P. Shen4, University of California Santa Cruz, Evan O. Paull5, Joshua M. Stuart5, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Andrew D. Cherniack6, Juok Cho6, Gad Getz6,7, Jaegil Kim6, Matthew Meyerson6,8, Bradley A. Murray6, Akinyemi I. Ojesina6,8, Chandra Sekhar Pedamallu6,8, Esther Rheinbay6,9, Mara W. Rosenberg6, Gordon Saksena6, Carrie Sougnez6, Chip Stewart6, Fred Hutchinson Cancer Research Center, Ni Zhao10, Department of Genetics, Harvard Medical School, Angela Hadjipanayis11,12, David J. Kwiatkowski13, University Health Network, Sylvia L. Asa14,15, Institute for Systems Biology, Lisa Iype16, The Johns Hopkins University School of Medicine, Justin A. Bishop17, Martha A. Zeiger18, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Leslie Cope18, Ludmila Danilova18, Christopher B. Umbricht17, Mayo Clinic, Robert C.

Sloan-Kettering Cancer Center, Giovanni Ciriello21, James A. Fagin22, Ian Ganly23, Ronald Ghossein24, Chris Sander21, Nikolaus Schultz21, Yasin Senbabaoglu21, Ronglai Shen25,

University of Michigan Health System, Thomas J. Giordano26,27, National Cancer Institute, Electron Kebebew28, Margi Sheth29, Jiashan (Julia) Zhang29, University of North Carolina at Chapel Hill, Katherine A. Hoadley31,32, Vonn Walter31, Matthew D. Wilkerson32 Ohio State University, Matthew D. Ringel33, University of Pittsburgh, Yuri E. Nikiforov34, The Research Institute at Nationwide Children's Hospital, Jay Bowen35, Kristen M. Leraas35, Tara M. Lichtenberg35, The University of Texas MD Anderson Cancer Center, Rehan Akbani36, Shiyun Ling36, Wenbin Liu36, Gordon Mills37, Alexei Protopopov38, John N. Weinstein36,37. Genome sequencing centers: Baylor College of Medicine, Kyle Covington39, Richard A. Gibbs39, David Wheeler39, Liu Xi39, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Chip Stewart6, Carrie Sougnez6, Kristian Cibulskis6, Lee Lichtenstein6, Timothy Fennell6, Sheila Fisher6, Stacey Gabriel6, Gad Getz6,7, Eric Lander6.

Genome characterization centers: BC Cancer Agency, Adrian Ally1, Miruna Balasundaram1, Reanne Bowlby1, Denise Brooks1, Yaron S.N. Butterfield1, Rebecca Carlsen1, Andy Chu1, Eric Chuah1, Dorothy Cheung1, Amanda Clarke1, Noreen Dhalla1, Ranabir Guin1, Robert A. Holt1, Steven J.M. Jones1, Katayoon Kasaian1, Darlene Lee1, Yussanne Ma1, Marco A. Marra1, Michael Mayo1, Richard A. Moore1, Andrew J. Mungall1, A. Gordon Robertson1, Sara Sadeghi1, Jacqueline E. Schein1, Payal Sipahimalani1, Angela Tam1, Nina Thiessen1; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Andrew D. Cherniack6, Bradley A. Murray6, Carrie Sougnez6 , Gordon Saksena6, Jonna

Grimsby6, Steven E. Schumacher6,69, Chandra Sekhar Pedamallu6.8, Barbara Tabak6,69, Travis I. Zack6,69, Scott L. Carter6, Gad Getz6,7, Rameen Beroukhim6,8,69,74, Levi A. Garraway6,8,76,

Sheliann S. Dookran6, Franklin W. Huang6,8,74, Stacey B. Gabriel6, Matthew Meyerson6,8,75, Harvard Medical School/Brigham & Women’s Hospital/MD Anderson Cancer Center, Semin Lee40, Angeliki Pantazi11, Xingzhi Song38, Lixing Yang40, Christopher A. Bristow38, Sahil Seth38, Andrew W. Xu40, Michael Parfenov11, Jiabin Tang38, Xiaojia Ren11, Harshad S.

Mahadeshwar38, Angela Hadjipanayis11,12, Eunjung Lee11,12, Netty Santoso11, Dong Zeng38, Alexei Protopopov38, Jianhua Zhang38, Jonathan Seidman11, Peter J. Park12,40, Lynda Chin6,38, and Raju Kucherlapati11,12, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Stephen B. Baylin18, Leslie Cope18, Ludmila Danilova18, James G. Herman18, University of North Carolina at Chapel Hill, J.Todd Auman41, Saianand Balu31, Tom Bodenheimer31, Elizabeth Buda42, Katherine A. Hoadley31,32, Alan P. Hoyle31, Stuart R. Jefferys31, Corbin D. Jones42,43, Shaowu Meng31, Piotr A. Mieczkowski32, Lisle E. Mose31, Charles M. Perou32,44, Jeffrey Roach45, Yan Shi31, Janae V. Simons31, Matthew G. Soloway31, Donghui Tan32, Umadevi Veluvolu32, Scot Waring31,42, Junyuan Wu31, University of Southern California Epigenome Center, David J. Van Den Berg46, Moiz S. Bootwalla46, Phillip H. Lai46, Peter W. Laird46, Daniel J. Weisenberger46, The University of Texas MD Anderson Cancer Center, Christopher A. Bristow38, Lynda Chin6,38, Harshad S. Mahadeshwar38, Alexei

Protopopov38, Sahil Seth38, Xingzhi Song38, Jiabin Tang38, Dong Zeng38, and Jianhua Zhang38. Genome data analysis centers: University of California San Francisco, Barry S. Taylor47, University of California Santa Cruz, Evan O. Paull5, Joshua M. Stuart5, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Gad Getz6,7, Chip Stewart6, Juok Cho6, Michael S. Noble6, Daniel DiCara6, Hailei Zhang6, David I. Heiman6, Nils Gehlenborg6,40, Lee Lichtenstein6, Gordon Saksena6, Doug Voet6, Harindra Arachchi6, Pei Lin6, Scott Frazer6, Petar Stojanov6,8, Yingchun Liu6, Lihua Zou6, Jaegil Kim6, Michael S. Lawrence6, Lynda Chin6,38, Fred Hutchinson Cancer Research Center, Ni Zhao10,

Institute for Systems Biology, Brady Bernard16, Lisa Iype16, Roger Kramer16, Richard Kreisberg16, Michael Miller16, Sheila M. Reynolds16, Ilya Shmulevich16, Vésteinn Thorsson16, University of Kentucky, Jinze Liu48, Memorial Sloan-Kettering Cancer Center, B. Arman Aksoy21, Giovanni Ciriello21, Gideon Dresdner21, Jianjiong Gao21, Benjamin Gross21, Anders Jacobsen21, Marc Ladanyi24, William Lee21, Ricardo Ramirez21, Chris Sander21, Nikolaus Schultz21, Yasin Senbabaoglu21, Ronglai Shen25, Rileen Sinha21, S. Onur Sumer21, Yichao Sun21, Nils Weinhold21, University of North Carolina at Chapel Hill, D. Neil Hayes31,49, Katherine A. Hoadley31, Joel S. Parker31,32, Jan F. Prins50, Vonn Walter31, Matthew D.

Wilkerson32, The University of Texas MD Anderson Cancer, Rehan Akbani36, Shiyun Ling36, Wenbin Liu36, Yiling Lu37, Gordon Mills37, John N. Weinstein36,37, Roel GW Verhaak36,51, Jianhua Zhang38, and Wei Zhang38.

Biospecimen core resource: The Research Institute at Nationwide Children's Hospital, Aaron D. Black35, Jay Bowen35, Robin Brookens35, Jessica Frick35, Julie M. Gastier-Foster35,52, Hollie A. Harper35, Kristen M. Leraas35, Tara M. Lichtenberg35, Nilsa C. Ramirez35,52, Samantha Sharpe35, Jocelyn Wilson35, Lisa Wise35, and Erik Zmuda35.

Tissue source sites: University Health Network, Sylvia L. Asa14,15, Daniel A. Winer14,15, Karen Gomez-Hernandez70, Johns Hopkins School of Medicine , Christopher B. Umbricht17, Martha A. Zeiger18, Justin Bishop17, Mayo Clinic, Robert C. Smallridge19, Michael Rivera53, Memorial Sloan-Kettering Cancer Center, Robert Bryant 54, Timothy A. Chan22, Stephanie Eng54, Ian Ganly23, Ronald Ghossein24, Matthew Rosenthal54 University of Michigan Health System, Michelle Vinco26, Thomas J. Giordano26,27, National Cancer Institute, Electron Kebebew28, University of North Carolina at Chapel Hill, J. Todd Auman41, Lori Boice31, Mei Huang31, W. Kimryn Rathmell31, Leigh Thorne44, and Ohio State University Matthew D.

Ringel33, University of Pittsburgh, Yuri E. Nikiforov34, Rajiv Dhir34, Raja R. Seethala34, Sally E. Carty68, Emory University, Taofeek K. Owonikoko71, Amy Y. Chen72, Gabriel L. Sica73, Fadlo R. Khuri71, Suresh S. Ramalingam71, Madhusmita Behera71., The University of Texas MD

Anderson Cancer, Adel K. El-Naggar62, Michelle D. Williams62, and Gary L. Clayman60.

Disease working groups: The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Carrie Sougnez6, Georgia Regents University, Paul M. Weinberger55, University Health Network Sylvia L. Asa14,15, Mayo Clinic, John A.

Copland56, Robert C. Smallridge19, Memorial Sloan-Kettering Cancer Center, Timothy A. Chan22, James A. Fagin22, Ian Ganly23, Ronald Ghossein24, R. Michael Tuttle57, University of Michigan, Thomas J. Giordano26,27, National Cancer Institute, Electron Kebebew28,

University of North Carolina at Chapel Hill, D. Neil Hayes31,49, Ohio State University, Matthew D. Ringel33, University of Pennsylvania, Virginia A. LiVolsi58, University of Pittsburgh, Robert L. Ferris59, Yuri E. Nikiforov34, Johns Hopkins University School of

Medicine, Nishant Agrawal18, Christopher B. Umbricht17, Martha A. Zeiger18 , The University of Texas MD Anderson Cancer, Adel K. El-Naggar62, Steven Sherman61, Michelle D. Williams62, University of Wisconsin, Ricardo V. Lloyd63, and Yale University School of Medicine Tobias Carling64.

Project team: National Cancer Institute, Tanja Davidsen29, John A. Demchok29, Greg Eley66, Kenna R. Mills Shaw30, Margi Sheth29, Roy Tarnuzzer29, Zhining Wang29, Liming Yang29, Jean Claude Zenklusen29, and National Human Genome Research Institute, Carolyn M. Hutter65, Bradley A. Ozenberger65,67, Heidi J. Sofia65.

Writing committee: T.J. Giordano, G. Getz, C. Stewart, J.A. Fagin, S.L. Asa, D.G. McFadden, Y.E. Nikiforov, M.D. Ringel, I. Ganly, R.C. Smallridge, and M.A. Zeiger.

Institutions

1 Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z, 4S6, Canada.

2 Brown University, Department of Computer Science, Providence, Rhode Island 02912, USA.

3 Department of Computer Science and Engineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

4 Departments of Medicine and Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093.

5 Department of Biomolecular Engineering and Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA.

6 The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, Massachusetts 02142, USA.

7 Massachusetts General Hospital Cancer Center and Department of Medicine,

Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 02114, USA.

8 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.

9 Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA.

10 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

11 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. 12 Division of Genetics, Brigham and Women’s Hospital, Boston, MA 02115, USA. 13 Division of Translational Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

14 Department of Pathology, University Health Network, Toronto, ON M5G 2C4 Canada. 15 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

16 Institute for Systems Biology, Seattle, WA 98109, USA.

17 The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

18 The S. Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA.

19 Endocrinology Division, Mayo Clinic, Jacksonville, FL, USA.

20 David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02142, USA.

21 Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

22 Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

23 Head and Neck Service, Dept. of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10022, USA.

24 Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.

25 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

26 Department of Pathology, University of Michigan Health System, Ann Arbor, MI, 48019, USA.

48109, USA.

28 Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

29 The Cancer Genome Atlas Program Office, Center for Cancer Genomics, National Cancer Institute, Bethesda, MD, USA.

30 Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, MD Anderson Cancer Center, Houston, TX 77030, USA.

31 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

32 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

33 Ohio State University College of Medicine and Arthur G. James Comprehensive Cancer Center, Columbus, OH 43210, USA.

34 Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

35 The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA. 36 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

37 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA.

38 Institute for Applied Cancer Science, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.

39 Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

40 The Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.

41 Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

42 Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

43 Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

44 Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, Chapel Hill, NC 27599, USA.

45 Research Computing Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

46 USC Epigenome Center, University of Southern California, Los Angeles, CA 90033, USA.

47 Helen Diller Family Comprehensive Cancer Center, University, San Francisco, CA 94143, USA.

48 Department of Computer Science, University of K., Lexington, KY 40506, USA.

49 Department of Internal Medicine, Department of Medical Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

50 Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

51 Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.

52 The Ohio State University, Columbus, OH 43210, USA. 53 Mayo Clinic, Rochester, MN 55905, USA

54 Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.

55 Department of Otolaryngology, Center for Biotechnology and Genomic Medicine, GRU Cancer Center, Georgia Regents University, Augusta, Georgia 30912, USA.

56 Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL, USA.

57 Endocrinology Service, Memorial Sloan Kettering Cancer Center, New York, NY, 10021, USA.

58 Department of Pathology and Laboratory Medicine, Hospital of University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.

59 Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.

60 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

61 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

62 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

63 Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, K4/436 CSC 8550, 600 Highland Ave., Madison, WI, 53792, USA. 64 Department of Surgery, Yale Endocrine Neoplasia Laboratory and Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA.

65 National Human Genome Research Institute, National Institute of Health, Bethesda, MD, 20892, USA.

66 TCGA Consultant, Scimentis, LLC, Atlanta, GA, USA.

67 The Genome Institute, Washington University, St Louis, Missouri 63108, USA. 68 Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.

69 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

70 Department of Medicine, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada.

71 Department of Hematology & Medical Oncology, Emory University and Winship Cancer Institute, Atlanta, GA 30322, USA.

72 Department of Otolaryngology Head & Neck Surgery, Emory University and Winship Cancer Institute, Atlanta, GA 30322, USA.

73 Department of Pathology, Emory University and Winship Cancer Institute, Atlanta, GA 30322, USA.

74 Department of Medicine, Harvard Medical School, Boston, MA 02215, USA. 75 Department of Pathology, Harvard Medical School, Boston, MA 02215, USA. 76 Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston MA, 02115, USA.