The Integrated Genomic Landscape of Thymic Epithelial Tumors
Authors: Milan Radovich, Curtis R. Pickering, Ina Felau, Gavin Ha, Hailei Zhang, Heejoon Jo, Katherine A. Hoadley, Pavana Anur, Jiexin Zhang, Mike McLellan, Reanne Bowlby, Thomas Matthew, Ludmila Danilova, Apurva M. Hegde, Jaegil Kim, Mark D.M. Leiserson, Geetika Sethi, Charles Lu, Michael Ryan, Xiaoping Su, Andrew D. Cherniack, Gordon Robertson, Rehan Akbani, Paul Spellman, John N. Weinstein, D. Neil Hayes, Ben Raphael, Tara Lichtenberg, Kristen Leraas, Jean Claude Zenklusen, Junya Fujimoto, Cristovam Scapulatempo-Neto, Andre L. Moreira, David Hwang, James Huang, Mirella Marino, Robert Korst, Giuseppe Giaccone, Yesim Gokmen-Polar, Sunil Badve, Arun Rajan, Philipp Ströbel, Nicolas Girard, Ming S. Tsao, Alexander Marx, Anne S. Tsao, Patrick J. Loehrer, Adrian Ally, Elizabeth L. Appelbaum, J. Todd Auman, Miruna Balasundaram, Saianand Balu, Madhusmita Behera, Rameen Beroukhim, Mario Berrios, Giovanni Blandino, Tom Bodenheimer, Moiz S. Bootwalla, Jay Bowen, Denise Brooks, Flavio M. Carcano, Rebecca Carlsen, Andre L. Carvalho, Patricia Castro, Lara Chalabreysse, Lynda Chin, Juok Cho, Gina Choe, Eric Chuah, Sudha Chudamani, Carrie Cibulskis, Leslie Cope, Matthew G. Cordes, Daniel Crain, Erin Curley, Timothy Defreitas, John A. Demchok, Frank Detterbeck, Noreen Dhalla, Hendrik Dienemann, W. Jeff Edenfield, Francesco Facciolo, Martin L. Ferguson, Scott Frazer, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Stacey B. Gabriel, Johanna Gardner, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, David I. Heiman, Shital Hobensack, Andrea Holbrook, Robert A. Holt, Alan P. Hoyle, Carolyn M. Hutter, Michael Ittmann, Stuart R. Jefferys, Corbin D. Jones, Steven J.M. Jones, Katayoon Kasaian, Jaegil Kim, Patrick K. Kimes, Phillip H. Lai, Peter W. Laird, Michael S. Lawrence, Pei Lin, Jia Liu, Laxmi Lolla, Yiling Lu, Yussanne Ma, Dennis T. Maglinte, David Mallery, Elaine R. Mardis, Marco A. Marra, Julie Martin, Michael Mayo, Sam Meier, Michael Meister, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, Christopher A. Miller, Gordon B. Mills, Richard A. Moore, Scott Morris, Lisle E. Mose, Thomas Muley, Andrew J. Mungall, Karen Mungall, Rashi Naresh, Yulia Newton, Michael S. Noble, Taofeek Owonikoko, Joel S. Parker, Joseph Paulaskis, Robert Penny, Charles M. Perou, Corinne Perrin, Todd Pihl, Amie Radenbaugh, Suresh Ramalingam, Nilsa Ramirez, Ralf Rieker, Jeffrey Roach, Sara Sadeghi, Gordon Saksena, Jacqueline E. Schein, Heather K. Schmidt, Steven E. Schumacher, Candace Shelton, Troy Shelton, Yan Shi, Juliann Shih, Gabriel Sica, Henrique C.S. Silveira, Janae V. Simons, Payal Sipahimalani, Tara Skelly, Heidi J. Sofia, Matthew G. Soloway, Joshua Stuart, Qiang Sun, Angela Tam, Donghui Tan, Roy Tarnuzzer, Nina Thiessen, David J. Van Den Berg, Mohammad A. Vasef, Umadevi Veluvolu, Doug Voet, Vonn Walter, Yunhu Wan, Zhining Wang, Arne Warth, Cleo-Aron Weis, Daniel J. Weisenberger, Matthew D. Wilkerson, Lisa Wise, Tina Wong, Hsin-Ta Wu, Ye Wu, Liming Yang, Jiashan Zhang, Erik Zmuda
Journal: Cancer Cell (2018)

Highlights•Multi-omics definition of four robust molecular TET subtypes associated with survival•Thymomas have the lowest mutational burden among adult cancers•Enrichment of HRAS, NRAS, TP53, and recurrent GTF2I mutations are observed•Expression of autoimmune targets and aneuploidy links thymoma to myasthenia gravisSummaryThymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy.Graphical abstract