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Artikel ; Online: Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

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 D M / 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 / Naresh, Rashi / Pihl, Todd / Sun, Qiang / Wan, Yunhu / Wu, Ye / Ally, Adrian / Balasundaram, Miruna / Balu, Saianand / Beroukhim, Rameen / Bodenheimer, Tom / Buhay, Christian / Butterfield, Yaron S N / Carlsen, Rebecca / Carter, Scott L / Chao, Hsu / Chuah, Eric / Clarke, Amanda / Covington, Kyle R / Dahdouli, Mahmoud / Dewal, Ninad / Dhalla, Noreen / Doddapaneni, Harsha V / Drummond, Jennifer A / Gabriel, Stacey B / Gibbs, Richard A / Guin, Ranabir / Hale, Walker / Hawes, Alicia / Hayes, D Neil / Holt, Robert A / Hoyle, Alan P / Jefferys, Stuart R / Jones, Steven J M / Jones, Corbin D / Kalra, Divya / Kovar, Christie / Lewis, Lora / Li, Jie / Ma, Yussanne / Marra, Marco A / Mayo, Michael / Meng, Shaowu / Meyerson, Matthew / Mieczkowski, Piotr A / Moore, Richard A / Morton, Donna / Mose, Lisle E / Mungall, Andrew J / Muzny, Donna / Parker, Joel S / Perou, Charles M / Roach, Jeffrey / Schein, Jacqueline E / Schumacher, Steven E / Shi, Yan / Simons, Janae V / Sipahimalani, Payal / Skelly, Tara / Soloway, Matthew G / Sougnez, Carrie / Tam, Angela / Tan, Donghui / Thiessen, Nina / Veluvolu, Umadevi / Wang, Min / Wilkerson, Matthew D / Wong, Tina / Wu, Junyuan / Xi, Liu / Zhou, Jane / Bedford, Jason / Chen, Fengju / Fu, Yao / Gerstein, Mark / Haussler, David / Kasaian, Katayoon / Lai, Phillip / Ling, Shiyun / Radenbaugh, Amie / Van Den Berg, David / Weinstein, John N / Zhu, Jingchun / Albert, Monique / Alexopoulou, Iakovina / Andersen, Jeremiah J / Auman, J Todd / Bartlett, John / Bastacky, Sheldon / Bergsten, Julie / Blute, Michael L / Boice, Lori / Bollag, Roni J / Boyd, Jeff / Castle, Erik / Chen, Ying-Bei / Cheville, John C / Curley, Erin / Davies, Benjamin / DeVolk, April / Dhir, Rajiv / Dike, Laura / Eckman, John / Engel, Jay / Harr, Jodi / Hrebinko, Ronald / Huang, Mei / Huelsenbeck-Dill, Lori / Iacocca, Mary / Jacobs, Bruce / Lobis, Michael / Maranchie, Jodi K / McMeekin, Scott / Myers, Jerome / Nelson, Joel / Parfitt, Jeremy / Parwani, Anil / Petrelli, Nicholas / Rabeno, Brenda / Roy, Somak / Salner, Andrew L / Slaton, Joel / Stanton, Melissa / Thompson, R Houston / Thorne, Leigh / Tucker, Kelinda / Weinberger, Paul M / Winemiller, Cynthia / Zach, Leigh Anne / Zuna, Rosemary

The New England journal of medicine

2016  Band 374, Heft 2, Seite(n) 135–145

Abstract: 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 ... ...

Abstract 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.).
Mesh-Begriff(e) Carcinoma, Papillary/genetics ; Carcinoma, Papillary/metabolism ; CpG Islands/physiology ; DNA Methylation ; Humans ; Kidney Neoplasms/genetics ; Kidney Neoplasms/metabolism ; MicroRNAs/chemistry ; Mutation ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Phenotype ; Proto-Oncogene Proteins c-met/chemistry ; Proto-Oncogene Proteins c-met/genetics ; Proto-Oncogene Proteins c-met/metabolism ; RNA, Messenger/chemistry ; RNA, Neoplasm/chemistry ; Sequence Analysis, RNA ; Signal Transduction/physiology
Chemische Substanzen MicroRNAs ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; RNA, Messenger ; RNA, Neoplasm ; MET protein, human (EC 2.7.10.1) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
Sprache Englisch
Erscheinungsdatum 2016-01-14
Erscheinungsland United States
Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID 207154-x
ISSN 1533-4406 ; 0028-4793
ISSN (online) 1533-4406
ISSN 0028-4793
DOI 10.1056/NEJMoa1505917
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