Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma
A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, TCGA Research Network, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman, Mohamed H Abdel-Rahman, Rehan Akbani, Adrian Ally, J Todd Auman, Ozgun Babur, Miruna Balasundaram, Saianand Balu, Christopher Benz, Rameen Beroukhim, Inanc Birol, Tom Bodenheimer, Jay Bowen, Reanne Bowlby, Christopher A Bristow, Denise Brooks, Rebecca Carlsen, Colleen M Cebulla, Matthew T Chang, Andrew D Cherniack, Lynda Chin, Juok Cho, Eric Chuah, Sudha Chudamani, Carrie Cibulskis, Kristian Cibulskis, Leslie Cope, Sarah E Coupland, Ludmila Danilova, Timothy Defreitas, John A Demchok, Laurence Desjardins, Noreen Dhalla, Bita Esmaeli, Ina Felau, Martin L Ferguson, Scott Frazer, Stacey B Gabriel, Julie M Gastier-Foster, Nils Gehlenborg, Mark Gerken, Jeffrey E Gershenwald, Gad Getz, Ewan A Gibb, Klaus G Griewank, Elizabeth A Grimm, D Neil Hayes, Apurva M Hegde, David I Heiman, Carmen Helsel, Julian M Hess, Katherine A Hoadley, Shital Hobensack, Robert A Holt, Alan P Hoyle, Xin Hu, Carolyn M Hutter, Martine J Jager, Stuart R Jefferys, Corbin D Jones, Steven J M Jones, Cyriac Kandoth, Katayoon Kasaian, Jaegil Kim, Patrick K Kimes, Melanie Kucherlapati, Raju Kucherlapati, Eric Lander, Michael S Lawrence, Alexander J Lazar, Semin Lee, Kristen M Leraas, Tara M Lichtenberg, Pei Lin, Jia Liu, Wenbin Liu, Laxmi Lolla, Yiling Lu, Lisa Iype, Yussanne Ma, Harshad S Mahadeshwar, Odette Mariani, Marco A Marra, Michael Mayo, Sam Meier, Shaowu Meng, Matthew Meyerson, Piotr A Mieczkowski, Gordon B Mills, Richard A Moore, Lisle E Mose, Andrew J Mungall, Karen L Mungall, Bradley A Murray, Rashi Naresh, Michael S Noble, Junna Oba, Angeliki Pantazi, Michael Parfenov, Peter J Park, Joel S Parker, Alexander Penson, Charles M Perou, Todd Pihl, Robert Pilarski, Alexei Protopopov, Amie Radenbaugh, Karan Rai, Nilsa C Ramirez, Xiaojia Ren, Sheila M Reynolds, Jeffrey Roach, A Gordon Robertson, Sergio Roman-Roman, Jason Roszik, Sara Sadeghi, Gordon Saksena, Xavier Sastre, Dirk Schadendorf, Jacqueline E Schein, Lynn Schoenfield, Steven E Schumacher, Jonathan Seidman, Sahil Seth, Geetika Sethi, Margi Sheth, Yan Shi, Carol Shields, Juliann Shih, Ilya Shmulevich, Janae V Simons, Arun D Singh, Payal Sipahimalani, Tara Skelly, Heidi Sofia, Matthew G Soloway, Xingzhi Song, Marc-Henri Stern, Joshua Stuart, Qiang Sun, Huandong Sun, Angela Tam, Donghui Tan, Ming Tang, Jiabin Tang, Roy Tarnuzzer, Barry S Taylor, Nina Thiessen, Vesteinn Thorsson, Kane Tse, Vladislav Uzunangelov, Umadevi Veluvolu, Roel G W Verhaak, Doug Voet, Vonn Walter, Yunhu Wan, Zhining Wang, John N Weinstein, Matthew D Wilkerson, Michelle D Williams, Lisa Wise, Scott E Woodman, Tina Wong, Ye Wu, Liming Yang, Lixing Yang, Christina Yau, Jean C Zenklusen, Jiashan Zhang, Hailei Zhang, Erik Zmuda, A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, TCGA Research Network, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman, Mohamed H Abdel-Rahman, Rehan Akbani, Adrian Ally, J Todd Auman, Ozgun Babur, Miruna Balasundaram, Saianand Balu, Christopher Benz, Rameen Beroukhim, Inanc Birol, Tom Bodenheimer, Jay Bowen, Reanne Bowlby, Christopher A Bristow, Denise Brooks, Rebecca Carlsen, Colleen M Cebulla, Matthew T Chang, Andrew D Cherniack, Lynda Chin, Juok Cho, Eric Chuah, Sudha Chudamani, Carrie Cibulskis, Kristian Cibulskis, Leslie Cope, Sarah E Coupland, Ludmila Danilova, Timothy Defreitas, John A Demchok, Laurence Desjardins, Noreen Dhalla, Bita Esmaeli, Ina Felau, Martin L Ferguson, Scott Frazer, Stacey B Gabriel, Julie M Gastier-Foster, Nils Gehlenborg, Mark Gerken, Jeffrey E Gershenwald, Gad Getz, Ewan A Gibb, Klaus G Griewank, Elizabeth A Grimm, D Neil Hayes, Apurva M Hegde, David I Heiman, Carmen Helsel, Julian M Hess, Katherine A Hoadley, Shital Hobensack, Robert A Holt, Alan P Hoyle, Xin Hu, Carolyn M Hutter, Martine J Jager, Stuart R Jefferys, Corbin D Jones, Steven J M Jones, Cyriac Kandoth, Katayoon Kasaian, Jaegil Kim, Patrick K Kimes, Melanie Kucherlapati, Raju Kucherlapati, Eric Lander, Michael S Lawrence, Alexander J Lazar, Semin Lee, Kristen M Leraas, Tara M Lichtenberg, Pei Lin, Jia Liu, Wenbin Liu, Laxmi Lolla, Yiling Lu, Lisa Iype, Yussanne Ma, Harshad S Mahadeshwar, Odette Mariani, Marco A Marra, Michael Mayo, Sam Meier, Shaowu Meng, Matthew Meyerson, Piotr A Mieczkowski, Gordon B Mills, Richard A Moore, Lisle E Mose, Andrew J Mungall, Karen L Mungall, Bradley A Murray, Rashi Naresh, Michael S Noble, Junna Oba, Angeliki Pantazi, Michael Parfenov, Peter J Park, Joel S Parker, Alexander Penson, Charles M Perou, Todd Pihl, Robert Pilarski, Alexei Protopopov, Amie Radenbaugh, Karan Rai, Nilsa C Ramirez, Xiaojia Ren, Sheila M Reynolds, Jeffrey Roach, A Gordon Robertson, Sergio Roman-Roman, Jason Roszik, Sara Sadeghi, Gordon Saksena, Xavier Sastre, Dirk Schadendorf, Jacqueline E Schein, Lynn Schoenfield, Steven E Schumacher, Jonathan Seidman, Sahil Seth, Geetika Sethi, Margi Sheth, Yan Shi, Carol Shields, Juliann Shih, Ilya Shmulevich, Janae V Simons, Arun D Singh, Payal Sipahimalani, Tara Skelly, Heidi Sofia, Matthew G Soloway, Xingzhi Song, Marc-Henri Stern, Joshua Stuart, Qiang Sun, Huandong Sun, Angela Tam, Donghui Tan, Ming Tang, Jiabin Tang, Roy Tarnuzzer, Barry S Taylor, Nina Thiessen, Vesteinn Thorsson, Kane Tse, Vladislav Uzunangelov, Umadevi Veluvolu, Roel G W Verhaak, Doug Voet, Vonn Walter, Yunhu Wan, Zhining Wang, John N Weinstein, Matthew D Wilkerson, Michelle D Williams, Lisa Wise, Scott E Woodman, Tina Wong, Ye Wu, Liming Yang, Lixing Yang, Christina Yau, Jean C Zenklusen, Jiashan Zhang, Hailei Zhang, Erik Zmuda
Abstract
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.
Keywords: EIF1AX; GNA11; GNAQ; SF3B1; SRSF2; TCGA; molecular subtypes; monosomy 3; noncoding RNA; uveal melanoma.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Source: PubMed