1. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma
- Author
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Thai H. Ho, Tina Wong, Donna Morton, Benjamin J. Raphael, Lora Lewis, Carrie Sougnez, Noreen Dhalla, Candace Shelton, Lori Boice, Bhavani Krishnan, J. Todd Auman, Joel Nelson, Jodi K. Maranchie, Saianand Balu, Chad J. Creighton, Min Wang, Brenda Ayala, Monique Albert, Maria Merino, Christopher J. Ricketts, Mark D.M. Leiserson, Michael Lobis, Nicholas J. Petrelli, Jiashan Zhang, Cynthia Winemiller, Angela Tam, Tom Bodenheimer, Payal Sipahimalani, Divya Kalra, W. Kimryn Rathmell, W. Troy Shelton, Amanda Clarke, David Mallery, Sudha Chudamani, Victor E. Reuter, Leigh Anne Zach, Laxmi Lolla, Kristen M. Leraas, Sara Sadeghi, Sabina Signoretti, Walker Hale, Janae V. Simons, Jeffrey Roach, Jie Li, Andrew J. Mungall, Roni J. Bollag, Adrian Ally, David Van Den Berg, Qiang Sun, Matthew G. Soloway, Ed Reznik, Joel Slaton, Laura S. Schmidt, Lisa Wise, R. Houston Thompson, Jingchun Zhu, Michael Mayo, Gordon B. Mills, Benjamin Davies, Ramaprasad Srinivasan, Donald P. Bottaro, Yan Shi, Nilsa C. Ramirez, Rashi Naresh, Yiling Lu, Peter W. Laird, Jeremiah J. Andersen, Richard A. Gibbs, Bradley A. Murray, Erik Zmuda, Kenneth Burnett, Steven E. Schumacher, Han Liang, Katherine A. Hoadley, Cathy D. Vocke, Toni K. Choueiri, Scott L. Carter, Scott McMeekin, Yussanne Ma, Joseph Paulauskis, Jerome Myers, Ronald L. Hrebinko, Phillip H. Lai, Leigh B. Thorne, Brian Shuch, Junyuan Wu, Katayoon Kasaian, Nandita Barnabas, Denise Brooks, Heidi J. Sofia, David A. Wheeler, Daniel J. Weisenberger, Nina Thiessen, Mark Gerken, A. Ari Hakimi, Yaron S.N. Butterfield, Mary Iacocca, Matthew Meyerson, John A. Demchok, Gordon Saksena, Tara Skelly, Corbin D. Jones, Abu Amar M. Al Mamun, Sheldon I. Bastacky, Liu Xi, Andrew Salner, Erik P. Castle, Samira A. Brooks, Miruna Balasundaram, D. Neil Hayes, George Thomas, Eric Chuah, Umadevi Veluvolu, Zhining Wang, Moiz S. Bootwalla, Rebecca Carlsen, Jun Li, Harsha Doddapaneni, Stephen B. Baylin, Eric M. Thompson, Hui Shen, Ying-Bei Chen, Shaowu Meng, Mei Huang, Jodi Harr, John Eckman, Robert Penny, Jia Liu, Laura Dike, Andrew K. Godwin, April DeVolk, Joel S. Parker, Alicia Hawes, Angela N. Brooks, Margi Sheth, Scott M. Haake, Paul M. Weinberger, Satish K. Tickoo, Reanne Bowlby, Kenna R. Mills Shaw, Stuart R. Jefferys, Erin Curley, Donna M. Muzny, Rajiv Dhir, Mark E. Sherman, Kelinda Tucker, Tracie Santos, John N. Weinstein, Kevin Lau, Rehan Akbani, Carl Simon Shelley, Kyle R. Covington, Bogdan Czerniak, Christie Kovar, Todd Pihl, Piotr A. Mieczkowski, Jean C. Zenklusen, Mark Gerstein, Johanna Gardner, William Y. Kim, Marco A. Marra, A. Gordon Robertson, Roy Tarnuzzer, W. Marston Linehan, Lori Huelsenbeck-Dill, Steven J.M. Jones, Hsu Chao, Eve Shinbrot, Somak Roy, Fengju Chen, Pavana Anur, Melissa T. Avedon, Jacqueline E. Schein, Anurag Sethi, Rosemary E. Zuna, James J. Hsieh, Shiyun Ling, Julien Baboud, Robert A. Holt, Suzanne S. Fei, Jay Bowen, Mahmoud Dahdouli, Yunhu Wan, Anil V. Parwani, Stacey Gabriel, Pheroze Tamboli, Jane Zhou, Alan P. Hoyle, Jay Engel, John Bartlett, Michael L. Blute, Peggy Yena, Richard A. Moore, Matthew D. Wilkerson, Christian J. Buhay, Andrew D. Cherniack, Rameen Beroukhim, Michael M. Ittmann, Laurence Albiges, Tara M. Lichtenberg, Julie Bergsten, Carolyn M. Hutter, Ranabir Guin, Yao Fu, Bruce L. Jacobs, Scott Morris, Jennifer Drummond, Brenda Rabeno, Ninad Dewal, Julie M. Gastier-Foster, Myron Peto, Caleb F. Davis, Daniel Crain, Iakovina Alexopoulou, John C. Cheville, Jason Bedford, Ina Felau, Donghui Tan, Liming Yang, David Haussler, Jeff Boyd, Charles M. Perou, Melissa L. Stanton, Ye Wu, Amie Radenbaugh, Paul T. Spellman, Lisle E. Mose, and Jeremy Parfitt
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,NF-E2-Related Factor 2 ,Disease ,urologic and male genital diseases ,Article ,Translational Research, Biomedical ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Surveys and Questionnaires ,medicine ,Carcinoma ,Humans ,RNA, Messenger ,RNA, Neoplasm ,Papillary renal cell carcinomas ,business.industry ,Sequence Analysis, RNA ,Cancer ,General Medicine ,DNA Methylation ,Proto-Oncogene Proteins c-met ,medicine.disease ,Carcinoma, Papillary ,Kidney Neoplasms ,MicroRNAs ,030104 developmental biology ,Phenotype ,030220 oncology & carcinogenesis ,Sporadic Papillary Renal Cell Carcinoma ,Mutation ,Hereditary leiomyomatosis and renal cell carcinoma ,CpG Islands ,business ,Signal Transduction - Abstract
Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist.We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis.Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH).Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).
- Published
- 2015