Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma
| Autor: | Cancer Genome Atlas Research Network, Linehan, W Marston, Spellman, Paul T, Ricketts, Christopher J, Creighton, Chad J, Fei, Suzanne S, Davis, Caleb, Wheeler, David A, Murray, Bradley A, Schmidt, Laura, Vocke, Cathy D, Peto, Myron, Al Mamun, Abu Amar M, Shinbrot, Eve, Sethi, Anurag, Brooks, Samira, Rathmell, W Kimryn, Brooks, Angela N, Hoadley, Katherine A, Robertson, A Gordon, Brooks, Denise, Bowlby, Reanne, Sadeghi, Sara, Shen, Hui, Weisenberger, Daniel J, Bootwalla, Moiz, Baylin, Stephen B, Laird, Peter W, Cherniack, Andrew D, Saksena, Gordon, Haake, Scott, Li, Jun, Liang, Han, Lu, Yiling, Mills, Gordon B, Akbani, Rehan, Leiserson, Mark DM, Raphael, Benjamin J, Anur, Pavana, Bottaro, Donald, Albiges, Laurence, Barnabas, Nandita, Choueiri, Toni K, Czerniak, Bogdan, Godwin, Andrew K, Hakimi, A Ari, Ho, Thai H, Hsieh, James, Ittmann, Michael, Kim, William Y, Krishnan, Bhavani, Merino, Maria J, Mills Shaw, Kenna R, Reuter, Victor E, Reznik, Ed, Shelley, Carl S, Shuch, Brian, Signoretti, Sabina, Srinivasan, Ramaprasad, Tamboli, Pheroze, Thomas, George, Tickoo, Satish, Burnett, Kenneth, Crain, Daniel, Gardner, Johanna, Lau, Kevin, Mallery, David, Morris, Scott, Paulauskis, Joseph D, Penny, Robert J, Shelton, Candace, Shelton, W Troy, Sherman, Mark, Thompson, Eric, Yena, Peggy, Avedon, Melissa T, Bowen, Jay, Gastier-Foster, Julie M, Gerken, Mark, Leraas, Kristen M, Lichtenberg, Tara M, Ramirez, Nilsa C, Santos, Tracie, Wise, Lisa, Zmuda, Erik, Demchok, John A, Felau, Ina, Hutter, Carolyn M, Sheth, Margi, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Ayala, Brenda, Baboud, Julien, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi |
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| Rok vydání: | 2016 |
| Předmět: |
Kidney Disease
NF-E2-Related Factor 2 Papillary Messenger Cancer Genome Atlas Research Network Medical and Health Sciences Rare Diseases General & Internal Medicine Genetics Humans Cancer Carcinoma DNA Methylation Proto-Oncogene Proteins c-met Kidney Neoplasms MicroRNAs Phenotype Good Health and Well Being Mutation RNA Neoplasm CpG Islands Digestive Diseases Sequence Analysis Signal Transduction Biotechnology |
| Zdroj: | The New England journal of medicine, vol 374, iss 2 |
| Popis: | BackgroundPapillary 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.MethodsWe 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.ResultsType 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).ConclusionsType 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.). |
| Databáze: | OpenAIRE |
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