Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

著者: Benjamin J. Raphael, Ralph H. Hruban, Andrew J. Aguirre, Richard A. Moffitt, Jen Jen Yeh, Chip Stewart, A. Gordon Robertson, Andrew D. Cherniack, Manaswi Gupta, Gad Getz, Stacey Gabriel, Matthew Meyerson, Carrie Cibulskis, Suzanne S. Fei, Toshinori Hinoue, Hui Shen, Peter W. Laird, Shiyun Ling, Yiling Lu, Gordon B. Mills, Rehan Akbani, Phillipe Loher, Eric Londin, Isidore Rigoutsos, Aristeidis G. Telonis, Ewan A. Gibb, Anna Goldenberg, Aziz M. Mezlini, Katherine A. Hoadley, Eric A. Collisson, Eric S. Lander, Bradley A. Murray, Julian M. Hess, Mara Rosenberg, Louis Bergelson, Hailei Zhang, Juok Cho, Grace Tiao, Jaegil Kim, Dimitri Livitz, Ignaty Leshchiner, Brendan Reardon, Eliezer M. Van Allen, Atanas Kamburov, Rameen Beroukhim, Gordon Saksena, Steven E. Schumacher, Michael S. Noble, David I. Heiman, Nils Gehlenborg, Jaegil Kim, Michael S. Lawrence, Volkan Adsay, Gloria M. Petersen, David S. Klimstra, Nabeel Bardeesy, Mark D.M. Leiserson, Reanne Bowlby, Katayoon Kasaian, İnanç Birol, Karen Mungall, Sara Sadeghi, John N. Weinstein, Paul T. Spellman, Yuexin Liu, Laufey T. Ámundadóttir, Joel E. Tepper, Aatur D. Singhi, Rajiv Dhir, Paul Drwiega, Thomas C. Smyrk, Lizhi Zhang, Paula Kim, Jay Bowen, Jessica Frick, Julie M. Gastier‐Foster, Mark Gerken, Kevin Lau, Kristen Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Jeremy Renkel, Mark E. Sherman, Lisa Wise, Peggy Yena, Erik Zmuda, Juliann Shih, Adrian Ally, Miruna Balasundaram, Rebecca Carlsen, Andy Chu, Eric Chuah, Amanda Clarke, Noreen Dhalla, Robert A. Holt, Steven J.M. Jones, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Denise Brooks, J. Todd Auman, Saianand Balu, Tom Bodenheimer, D. Neil Hayes, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Charles M. Perou, Amy H. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Joel S. Parker, Matthew D. Wilkerson, Anil Korkut, Yasin Şenbabaoğlu, Patrick A. Burch, Robert R. McWilliams, Kari G. Chaffee, Ann L. Oberg, Wei Zhang, Marie‐Claude Gingras, David A. Wheeler, Xi Liu, Monique Albert, John M.S. Bartlett, Harman Sekhon, Yeager Stephen, Zaren Howard, Judy Miller, Anne Breggia, Rachna T. Shroff, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Smith Jennifer, Kevin K. Roggin, Karl‐Friedrich Becker, Madhusmita Behera, Joseph Bennett, Lori Boice, Eric Burks, Carlos Gilberto Carlotti, John A. Chabot, Daniela Pretti da Cunha Tirapelli, José Sebastião dos Santos, Michael Dubina, Jennifer Eschbacher, Mei Huang, Lori Huelsenbeck-Dill, Roger Jenkins, А. А. Карпов, Rafael Kemp, Vladimir Lyadov, Shishir K. Maithel, Georgy M. Manikhas, Eric Montgomery, Houtan Noushmehr, Adeboye O. Osunkoya, Taofeek K. Owonikoko, Oxana Paklina, Olga Potapova, Suresh Ramalingam, W. Kimryn Rathmell, Kimberly Rieger‐Christ, Charles Saller, Galiya Setdikova, Shabunin Av, Gabriel Sica, Tao Su, Travis Sullivan, Pat Swanson, Katherine Tarvin, Michael Tavobilov, Leigh B. Thorne, Stefan J. Urbanski, Olga Voronina, Timothy C. Wang, Daniel Crain, Erin Curley, Johanna Gardner, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Klaus‐Peter Janssen, Oliver F. Bathe, Nathan Bahary, Julia Slotta‐Huspenina, Amber L. Johns, Hanina Hibshoosh, Rosa F. Hwang, Antonia R. Sepulveda, Amie Radenbaugh, Stephen B. Baylin, Mario Berríos, Moiz S. Bootwalla, Andrea Holbrook, Phillip H. Lai, Dennis T. Maglinte, Swapna Mahurkar‐Joshi, Timothy J. Triche, David Van Den Berg, Daniel J. Weisenberger, Lynda Chin, Raju Kucherlapati, Melanie H. Kucherlapati, Angeliki Pantazi, Peter J. Park, Gordon Saksena, Doug Voet, Pei Lin, Scott Frazer, Timothy Defreitas, Sam Meier, Lynda Chin, Sun Young Kwon, Yong‐Hoon Kim, Sang‐Jae Park, Sung‐Sik Han, Seong Hoon Kim, Hark Kyun Kim, Emma E. Furth, Margaret A. Tempero, Chris Sander, Andrew V. Biankin, David K. Chang, Peter J. Bailey, Anthony J. Gill, James G. Kench, Sean M. Grimmond, Amber L. Johns, Australian Pancreatic Cancer Genome Initiative Apgi, Russell G. Postier, Rosemary E. Zuna, Hugues Sicotte, John A. Demchok, Martin L. Ferguson, Carolyn M. Hutter, Kenna Shaw, Margi Sheth, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jiashan Zhang, Ina Felau, Jean C. Zenklusen - Cancer Cell 2017 被引用: 2,069

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.