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Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.
228 auth. W. Linehan, P. Spellman, C. Ricketts, C. Creighton, S. Fei, Caleb F. Davis, D. Wheeler, Bradley A. Murray, L. Schmidt, C. Vocke, Myron Peto, A. A. M. Al Mamun, E. Shinbrot, A. Sethi, S. Brooks, ... W. Rathmell, Angela N. Brooks, K. Hoadley, A. G. Robertson, Denise Brooks, R. Bowlby, S. Sadeghi, Hui Shen, D. Weisenberger, Moiz Bootwalla, S. Baylin, P. Laird, A. Cherniack, G. Saksena, S. Haake, Jun Li, Han Liang, Yiling Lu, G. Mills, Rehan Akbani, Mark D. M. Leiserson, Benjamin J. Raphael, Pavana Anur, D. Bottaro, L. Albiges, N. Barnabas, T. Choueiri, B. Czerniak, A. Godwin, A. Hakimi, T. Ho, J. Hsieh, M. Ittmann, William Y. Kim, B. Krishnan, M. Merino, K. R. Mills Shaw, V. Reuter, E. Reznik, C. Shelley, B. Shuch, S. Signoretti, R. Srinivasan, P. Tamboli, G. Thomas, S. Tickoo, K. Burnett, D. Crain, J. Gardner, Kevin R Lau, D. Mallery, S. Morris, J. Paulauskis, R. Penny, C. Shelton, W. T. Shelton, M. Sherman, E. Thompson, P. Yena, Melissa Avedon, Jay Bowen, J. Gastier-Foster, M. Gerken, K. Leraas, T. Lichtenberg, N. Ramirez, T. Santos, L. Wise, E. Zmuda, John A. Demchok, Ina Felau, C. Hutter, Margi Sheth, H. Sofia, R. Tarnuzzer, Zhining Wang, Liming Yang, J. Zenklusen, J. Zhang, Brenda Ayala, J. Baboud, Sudha Chudamani, Jia Liu, Laxmi Lolla, R. Naresh, T. Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Adrian Ally, M. Balasundaram, S. Balu, R. Beroukhim, T. Bodenheimer, C. Buhay, Y. Butterfield, R. Carlsen, S. Carter, H. Chao, E. Chuah, A. Clarke, K. Covington, M. Dahdouli, N. Dewal, Noreen Dhalla, H. Doddapaneni, J. Drummond, S. Gabriel, R. Gibbs, R. Guin, Walker Hale, A. Hawes, D. Hayes, R. Holt, A. Hoyle, S. Jefferys, Steven J. M. Jones, Corbin D. Jones, D. Kalra, C. Kovar, L. Lewis, Jie Li, Yussanne Ma, M. Marra, Michael Mayo, S. Meng, M. Meyerson, P. Mieczkowski, Richard A. Moore, Donna Morton, Lisle E. Mose, A. Mungall, D. Muzny, J. Parker, C. Perou, J. Roach, J. Schein, S. Schumacher, Yan Shi, J. Simons, Payal Sipahimalani, Tara J. Skelly, Matthew G. Soloway, C. Sougnez, Angela Tam, Donghui Tan, N. Thiessen, Umadevi Veluvolu, Min Wang, M. Wilkerson, Tina Wong, Junyuan Wu, Liu Xi, Jane H. Zhou, Jason Bedford, Fengju Chen, Yao Fu, M. Gerstein, D. Haussler, K. Kasaian, Phillip H. Lai, Shiyun Ling, Amie Radenbaugh, D. J. Van Den Berg, J. Weinstein, Jingchun Zhu, Monique Albert, I. Alexopoulou, Jeremiah J. Andersen, J. Auman, J. Bartlett, S. Bastacky, Julie Bergsten, M. Blute, L. Boice, R. Bollag, J. Boyd, E. Castle, Ying-bei Chen, J. Cheville, Erin E. Curley, B. Davies, April DeVolk, R. Dhir, Laura Dike, J. Eckman, J. Engel, Jodi Harr, R. Hrebinko, Meijuan Huang, L. Huelsenbeck-Dill, M. Iacocca, B. Jacobs, M. Lobis, J. Maranchie, S. McMeekin, J. Myers, J. Nelson, J. Parfitt, A. Parwani, N. Petrelli, B. Rabeno, Somak Roy, A. Salner, J. Slaton, M. Stanton, R. Thompson, L. Thorne, Kelinda Tucker, P. Weinberger, C. Winemiller, L. A. Zach, R. Zuna
BACKGROUND 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 …
BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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 in New England Journal of Medicine
146
 10 2016