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Integrated Molecular Characterization of Testicular Germ Cell Tumors

2018; Cell Press; Volume: 23; Issue: 11 Linguagem: Inglês

10.1016/j.celrep.2018.05.039

2639-1856

Hui Shen, Juliann Shih, Daniel P. Hollern, Linghua Wang, Reanne Bowlby, Satish K. Tickoo, Vésteinn Thórsson, Andrew J. Mungall, Yulia Newton, Apurva M. Hegde, Joshua Armenia, Francisco Sánchez-Vega, John Pluta, Louise C. Pyle, Rohit Mehra, Victor E. Reuter, Guilherme Godoy, Jeffrey Jones, Carl Simon Shelley, Darren R. Feldman, Daniel Onofre Vidal, Davor Lessel, Tomislav Kuliš, Flavio Mavignier Cárcano, Kristen Leraas, Tara M. Lichtenberg, Denise Brooks, Andrew D. Cherniack, Juok Cho, David I. Heiman, L. Sylvia, Minwei Liu, Michael S. Noble, Xi Liu, Hailei Zhang, Wanding Zhou, Jean C. Zenklusen, Carolyn M. Hutter, Ina Felau, Jiashan Zhang, Nikolaus Schultz, Gad Getz, Matthew Meyerson, Joshua M. Stuart, Rehan Akbani, David A. Wheeler, Peter W. Laird, Katherine L. Nathanson, Victoria K. Cortessis, Katherine A. Hoadley, Linghua Wang, Xi Liu, David A. Wheeler, Daniel Hughes, Kyle R. Covington, Joy C. Jayaseelan, Viktoriya Korchina, Lora Lewis, Hai Hu, HarshaVardhan Doddapaneni, Donna M. Muzny, Richard A. Gibbs, Katherine A. Hoadley, Daniel P. Hollern, Benjamin G. Vincent, Shengjie Chai, Christof C. Smith, J. Todd Auman, Yan Shi, Shaowu Meng, Tara Skelly, Donghui Tan, Umadevi Veluvolu, Piotr A. Mieczkowski, Corbin D. Jones, Matthew D. Wilkerson, Saianand Balu, Tom Bodenheimer, Alan P. Hoyle, Joshua M. Stuart, Lisle E. Mose, Janae V. Simons, Matthew G. Soloway, Jeffrey Roach, Joel S. Parker, D. Neil Hayes, Charles M. Perou, Juliann Shih, Andrew D. Cherniack, Matthew Meyerson, Gordon Saksena, Carrie Cibulskis, Steven E. Schumacher, Rameen Beroukhim, Stacey Gabriel, Reanne Bowlby, Andrew J. Mungall, Denise Brooks, L. Sylvia, Adrian Ally, Miruna Balasundaram, Rebecca Carlsen, Dorothy Cheung, Eric Chuah, Noreen Dhalla, Robert A. Holt, Steven J.M. Jones, Yussanne Ma, Michael Mayo, Richard A. Moore, A. Gordon Robertson, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Tina Wong, Marco A. Marra, Hui Shen, Wanding Zhou, Peter W. Laird, Daniel J. Weisenberger, David Van Den Berg, Phillip H. Lai, Mario Berríos, Andrea Holbrook, Arnoud Boot, Dennis T. Maglinte, Joshua Armenia, Francisco Sánchez-Vega, Nikolaus Schultz, Debyani Chakravarty, Jianjiong Gao, Zachary Heins, Ritika Kundra, Angelica Ochoa, Minwei Liu, Chris Sander, Marc Ladanyi, Vésteinn Thórsson, Amie Radenbaugh, Yulia Newton, Joshua M. Stuart, Juok Cho, David I. Heiman, Michael S. Noble, Hailei Zhang, Gad Getz, Nils Gehlenborg, Gordon Saksena, Doug Voet, Pei Lin, Scott Frazer, Seungchan Kim, Michael S. Lawrence, Thomas J. Giordano, Timothy Defreitas, Lynda Chin, Apurva M. Hegde, Rehan Akbani, John N. Weinstein, Wenbin Liu, Gordon B. Mills, Yiling Lu, Louise C. Pyle, John Pluta, Katherine L. Nathanson, Satish K. Tickoo, Victor E. Reuter, Rohit Mehra, Leendert H. J. Looijenga, Alan H. Bryce, Flavio Mavignier Cárcano, André Lopes Carvalho, Victoria K. Cortessis, Darren R. Feldman, Guilherme Godoy, Michael Ittmann, Jeffrey Jones, Tomislav Kuliš, Seth P. Lerner, Davor Lessel, Katherine L. Nathanson, Carl Simon Shelley, Daniel Onofre Vidal, Kristen Leraas, Tara M. Lichtenberg, Jay Bowen, Julie M. Gastier‐Foster, Mark Gerken, Carmen Helsel, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Sandra Cottingham, David Chesla, Charles Saller, Katherine Tarvin, Luiz Fernando Lopes, Cristovam Scapulatempo‐Neto, Natália D. Aredes, Wolter Oosterhuis, Ad Gillis, Hans Stoop, W M H Eijkenboom, George Sandusky, Sue Martin, Manju Aron, Siamak Daneshmand, Hooman Djaladat, David I. Quinn, Tanya B. Dorff, Jochen K. Lennerz, Leigh B. Thorne, Marija Gamulin, Željko Kaštelan, Tvrtko Hudolin, Christian Kubisch, Lori Boice, Mei Huang, Amy H. Perou, W. Kimryn Rathmell, Todd Pihl, Yunhu Wan, Qiang Sun, Rashi Naresh, Sudha Chudamani, Jia Liu, Laxmi Lolla, Ye Wu, Martin L. Ferguson, Jean C. Zenklusen, Ina Felau, Jiashan Zhang, Margi Sheth, John A. Demchok, Liming Yang, Linghua Wang, Roy Tarnuzzer, Carolyn M. Hutter, Heidi J. Sofia, Tanja M. Davidsen,

Renal and related cancers

We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance—KIT, KRAS, and NRAS—exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas.