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Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma
- Robertson, A Gordon;
- Shih, Juliann;
- Yau, Christina;
- Gibb, Ewan A;
- Oba, Junna;
- Mungall, Karen L;
- Hess, Julian M;
- Uzunangelov, Vladislav;
- Walter, Vonn;
- Danilova, Ludmila;
- Lichtenberg, Tara M;
- Kucherlapati, Melanie;
- Kimes, Patrick K;
- Tang, Ming;
- Penson, Alexander;
- Babur, Ozgun;
- Akbani, Rehan;
- Bristow, Christopher A;
- Hoadley, Katherine A;
- Iype, Lisa;
- Chang, Matthew T;
- Network, TCGA Research;
- Abdel-Rahman, Mohamed H;
- Akbani, Rehan;
- Ally, Adrian;
- Auman, J Todd;
- Babur, Ozgun;
- Balasundaram, Miruna;
- Balu, Saianand;
- Benz, Christopher;
- Beroukhim, Rameen;
- Birol, Inanc;
- Bodenheimer, Tom;
- Bowen, Jay;
- Bowlby, Reanne;
- Bristow, Christopher A;
- Brooks, Denise;
- Carlsen, Rebecca;
- Cebulla, Colleen M;
- Chang, Matthew T;
- Cherniack, Andrew D;
- Chin, Lynda;
- Cho, Juok;
- Chuah, Eric;
- Chudamani, Sudha;
- Cibulskis, Carrie;
- Cibulskis, Kristian;
- Cope, Leslie;
- Coupland, Sarah E;
- Danilova, Ludmila;
- Defreitas, Timothy;
- Demchok, John A;
- Desjardins, Laurence;
- Dhalla, Noreen;
- Esmaeli, Bita;
- Felau, Ina;
- Ferguson, Martin L;
- Frazer, Scott;
- Gabriel, Stacey B;
- Gastier-Foster, Julie M;
- Gehlenborg, Nils;
- Gerken, Mark;
- Gershenwald, Jeffrey E;
- Getz, Gad;
- Gibb, Ewan A;
- Griewank, Klaus G;
- Grimm, Elizabeth A;
- Hayes, D Neil;
- Hegde, Apurva M;
- Heiman, David I;
- Helsel, Carmen;
- Hess, Julian M;
- Hoadley, Katherine A;
- Hobensack, Shital;
- Holt, Robert A;
- Hoyle, Alan P;
- Hu, Xin;
- Hutter, Carolyn M;
- Jager, Martine J;
- Jefferys, Stuart R;
- Jones, Corbin D;
- Jones, Steven JM;
- Kandoth, Cyriac;
- Kasaian, Katayoon;
- Kim, Jaegil;
- Kimes, Patrick K;
- Kucherlapati, Melanie;
- Kucherlapati, Raju;
- Lander, Eric;
- Lawrence, Michael S;
- Lazar, Alexander J;
- Lee, Semin;
- Leraas, Kristen M;
- Lichtenberg, Tara M;
- Lin, Pei;
- Liu, Jia;
- Liu, Wenbin;
- Lolla, Laxmi;
- Lu, Yiling;
- Iype, Lisa;
- Ma, Yussanne;
- Mahadeshwar, Harshad S;
- Mariani, Odette;
- Marra, Marco A;
- Mayo, Michael;
- Meier, Sam;
- Meng, Shaowu;
- Meyerson, Matthew;
- Mieczkowski, Piotr A;
- Mills, Gordon B;
- Moore, Richard A;
- Mose, Lisle E;
- Mungall, Andrew J;
- Mungall, Karen L;
- Murray, Bradley A;
- Naresh, Rashi;
- Noble, Michael S;
- Oba, Junna;
- Pantazi, Angeliki;
- Parfenov, Michael;
- Park, Peter J;
- Parker, Joel S;
- Penson, Alexander;
- Perou, Charles M;
- Pihl, Todd;
- Pilarski, Robert;
- Protopopov, Alexei;
- Radenbaugh, Amie;
- Rai, Karan;
- Ramirez, Nilsa C;
- Ren, Xiaojia;
- Reynolds, Sheila M;
- Roach, Jeffrey;
- Robertson, A Gordon;
- Roman-Roman, Sergio;
- Roszik, Jason;
- Sadeghi, Sara;
- Saksena, Gordon;
- Sastre, Xavier;
- Schadendorf, Dirk;
- Schein, Jacqueline E;
- Schoenfield, Lynn;
- Schumacher, Steven E;
- Seidman, Jonathan;
- Seth, Sahil;
- Sethi, Geetika;
- Sheth, Margi;
- Shi, Yan;
- Shields, Carol;
- Shih, Juliann;
- Shmulevich, Ilya;
- Simons, Janae V;
- Singh, Arun D;
- Sipahimalani, Payal;
- Skelly, Tara;
- Sofia, Heidi;
- Soloway, Matthew G;
- Song, Xingzhi;
- Stern, Marc-Henri;
- Stuart, Joshua;
- Sun, Qiang;
- Sun, Huandong;
- Tam, Angela;
- Tan, Donghui;
- Tang, Ming;
- Tang, Jiabin;
- Tarnuzzer, Roy;
- Taylor, Barry S;
- Thiessen, Nina;
- Thorsson, Vesteinn;
- Tse, Kane;
- Uzunangelov, Vladislav;
- Veluvolu, Umadevi;
- Verhaak, Roel GW;
- Voet, Doug;
- Walter, Vonn;
- Wan, Yunhu;
- Wang, Zhining;
- Weinstein, John N;
- Wilkerson, Matthew D;
- Williams, Michelle D;
- Wise, Lisa;
- Woodman, Scott E;
- Wong, Tina;
- Wu, Ye;
- Yang, Liming;
- Yang, Lixing;
- Yau, Christina;
- Zenklusen, Jean C;
- Zhang, Jiashan;
- Zhang, Hailei;
- Zmuda, Erik;
- Cherniack, Andrew D;
- Benz, Christopher;
- Mills, Gordon B;
- Verhaak, Roel GW;
- Griewank, Klaus G;
- Felau, Ina;
- Zenklusen, Jean C;
- Gershenwald, Jeffrey E;
- Schoenfield, Lynn;
- Lazar, Alexander J;
- Abdel-Rahman, Mohamed H;
- Roman-Roman, Sergio;
- Stern, Marc-Henri;
- Cebulla, Colleen M;
- Williams, Michelle D;
- Jager, Martine J;
- Coupland, Sarah E;
- Esmaeli, Bita;
- Kandoth, Cyriac;
- Woodman, Scott E
- et al.
Published Web Location
https://doi.org/10.1016/j.ccell.2017.07.003Abstract
Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.
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