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 IypeMatthew T. Chang, 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, Gordon Mills, 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, 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

Research output: Contribution to journalArticle

130 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)204-220.e15
JournalCancer Cell
Volume32
Issue number2
DOIs
StatePublished - Aug 14 2017

Fingerprint

Monosomy
DNA Methylation
Mutation
Uveal melanoma
Neoplasms

Keywords

  • EIF1AX
  • GNA11
  • GNAQ
  • molecular subtypes
  • monosomy 3
  • noncoding RNA
  • SF3B1
  • SRSF2
  • TCGA
  • uveal melanoma

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Robertson, A. G., Shih, J., Yau, C., Gibb, E. A., Oba, J., Mungall, K. L., ... Woodman, S. E. (2017). Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma. Cancer Cell, 32(2), 204-220.e15. https://doi.org/10.1016/j.ccell.2017.07.003

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.; 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 J.M.; 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; Mills, Gordon; 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 G.W.; 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 G.W.; 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.

In: Cancer Cell, Vol. 32, No. 2, 14.08.2017, p. 204-220.e15.

Research output: Contribution to journalArticle

Robertson, AG, Shih, J, Yau, C, Gibb, EA, Oba, J, Mungall, KL, Hess, JM, Uzunangelov, V, Walter, V, Danilova, L, Lichtenberg, TM, Kucherlapati, M, Kimes, PK, Tang, M, Penson, A, Babur, O, Akbani, R, Bristow, CA, Hoadley, KA, Iype, L, Chang, MT, Abdel-Rahman, MH, Akbani, R, Ally, A, Auman, JT, Babur, O, Balasundaram, M, Balu, S, Benz, C, Beroukhim, R, Birol, I, Bodenheimer, T, Bowen, J, Bowlby, R, Bristow, CA, Brooks, D, Carlsen, R, Cebulla, CM, Chang, MT, Cherniack, AD, Chin, L, Cho, J, Chuah, E, Chudamani, S, Cibulskis, C, Cibulskis, K, Cope, L, Coupland, SE, Danilova, L, Defreitas, T, Demchok, JA, Desjardins, L, Dhalla, N, Esmaeli, B, Felau, I, Ferguson, ML, Frazer, S, Gabriel, SB, Gastier-Foster, JM, Gehlenborg, N, Gerken, M, Gershenwald, JE, Getz, G, Gibb, EA, Griewank, KG, Grimm, EA, Hayes, DN, Hegde, AM, Heiman, DI, Helsel, C, Hess, JM, Hoadley, KA, Hobensack, S, Holt, RA, Hoyle, AP, Hu, X, Hutter, CM, Jager, MJ, Jefferys, SR, Jones, CD, Jones, SJM, Kandoth, C, Kasaian, K, Kim, J, Kimes, PK, Kucherlapati, M, Kucherlapati, R, Lander, E, Lawrence, MS, Lazar, AJ, Lee, S, Leraas, KM, Lichtenberg, TM, Lin, P, Liu, J, Liu, W, Mills, G, Lu, Y, Iype, L, Ma, Y, Mahadeshwar, HS, Mariani, O, Marra, MA, Mayo, M, Meier, S, Meng, S, Meyerson, M, Mieczkowski, PA, Mills, GB, Moore, RA, Mose, LE, Mungall, AJ, Mungall, KL, Murray, BA, Naresh, R, Noble, MS, Oba, J, Pantazi, A, Parfenov, M, Park, PJ, Parker, JS, Penson, A, Perou, CM, Pihl, T, Pilarski, R, Protopopov, A, Radenbaugh, A, Rai, K, Ramirez, NC, Ren, X, Reynolds, SM, Roach, J, Robertson, AG, Roman-Roman, S, Roszik, J, Sadeghi, S, Saksena, G, Sastre, X, Schadendorf, D, Schein, JE, Schoenfield, L, Schumacher, SE, Seidman, J, Seth, S, Sethi, G, Sheth, M, Shi, Y, Shields, C, Shih, J, Shmulevich, I, Simons, JV, Singh, AD, Sipahimalani, P, Skelly, T, Sofia, H, Soloway, MG, Song, X, Stern, MH, Stuart, J, Sun, Q, Sun, H, Tam, A, Tan, D, Tang, M, Tang, J, Tarnuzzer, R, Taylor, BS, Thiessen, N, Thorsson, V, Tse, K, Uzunangelov, V, Veluvolu, U, Verhaak, RGW, Voet, D, Walter, V, Wan, Y, Wang, Z, Weinstein, JN, Wilkerson, MD, Williams, MD, Wise, L, Woodman, SE, Wong, T, Wu, Y, Yang, L, Yang, L, Yau, C, Zenklusen, JC, Zhang, J, Zhang, H, Zmuda, E, Cherniack, AD, Benz, C, Mills, GB, Verhaak, RGW, Griewank, KG, Felau, I, Zenklusen, JC, Gershenwald, JE, Schoenfield, L, Lazar, AJ, Abdel-Rahman, MH, Roman-Roman, S, Stern, MH, Cebulla, CM, Williams, MD, Jager, MJ, Coupland, SE, Esmaeli, B, Kandoth, C & Woodman, SE 2017, 'Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma', Cancer Cell, vol. 32, no. 2, pp. 204-220.e15. https://doi.org/10.1016/j.ccell.2017.07.003
Robertson AG, Shih J, Yau C, Gibb EA, Oba J, Mungall KL et al. Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma. Cancer Cell. 2017 Aug 14;32(2):204-220.e15. https://doi.org/10.1016/j.ccell.2017.07.003
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. ; 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 J.M. ; 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 ; Mills, Gordon ; 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 G.W. ; 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 G.W. ; 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. / Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma. In: Cancer Cell. 2017 ; Vol. 32, No. 2. pp. 204-220.e15.
@article{f4593816feb84d419b2d01cb7c12799e,
title = "Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma",
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, molecular subtypes, monosomy 3, noncoding RNA, SF3B1, SRSF2, TCGA, uveal melanoma",
author = "Robertson, {A. Gordon} and Juliann Shih and Christina Yau and Gibb, {Ewan A.} and Junna Oba and Mungall, {Karen L.} and Hess, {Julian M.} and Vladislav Uzunangelov and Vonn Walter and Ludmila Danilova and Lichtenberg, {Tara M.} and Melanie Kucherlapati and Kimes, {Patrick K.} and Ming Tang and Alexander Penson and Ozgun Babur and Rehan Akbani and Bristow, {Christopher A.} and Hoadley, {Katherine A.} and Lisa Iype and Chang, {Matthew T.} and Abdel-Rahman, {Mohamed H.} and Rehan Akbani and Adrian Ally and Auman, {J. Todd} and Ozgun Babur and Miruna Balasundaram and Saianand Balu and Christopher Benz and Rameen Beroukhim and Inanc Birol and Tom Bodenheimer and Jay Bowen and Reanne Bowlby and Bristow, {Christopher A.} and Denise Brooks and Rebecca Carlsen and Cebulla, {Colleen M.} and Chang, {Matthew T.} and Cherniack, {Andrew D.} and Lynda Chin and Juok Cho and Eric Chuah and Sudha Chudamani and Carrie Cibulskis and Kristian Cibulskis and Leslie Cope and Coupland, {Sarah E.} and Ludmila Danilova and Timothy Defreitas and Demchok, {John A.} and Laurence Desjardins and Noreen Dhalla and Bita Esmaeli and Ina Felau and Ferguson, {Martin L.} and Scott Frazer and Gabriel, {Stacey B.} and Gastier-Foster, {Julie M.} and Nils Gehlenborg and Mark Gerken and Gershenwald, {Jeffrey E.} and Gad Getz and Gibb, {Ewan A.} and Griewank, {Klaus G.} and Grimm, {Elizabeth A.} and Hayes, {D. Neil} and Hegde, {Apurva M.} and Heiman, {David I.} and Carmen Helsel and Hess, {Julian M.} and Hoadley, {Katherine A.} and Shital Hobensack and Holt, {Robert A.} and Hoyle, {Alan P.} and Xin Hu and Hutter, {Carolyn M.} and Jager, {Martine J.} and Jefferys, {Stuart R.} and Jones, {Corbin D.} and Jones, {Steven J.M.} and Cyriac Kandoth and Katayoon Kasaian and Jaegil Kim and Kimes, {Patrick K.} and Melanie Kucherlapati and Raju Kucherlapati and Eric Lander and Lawrence, {Michael S.} and Lazar, {Alexander J.} and Semin Lee and Leraas, {Kristen M.} and Lichtenberg, {Tara M.} and Pei Lin and Jia Liu and Wenbin Liu and Gordon Mills and Yiling Lu and Lisa Iype and Yussanne Ma and Mahadeshwar, {Harshad S.} and Odette Mariani and Marra, {Marco A.} and Michael Mayo and Sam Meier and Shaowu Meng and Matthew Meyerson and Mieczkowski, {Piotr A.} and Mills, {Gordon B.} and Moore, {Richard A.} and Mose, {Lisle E.} and Mungall, {Andrew J.} and Mungall, {Karen L.} and Murray, {Bradley A.} and Rashi Naresh and Noble, {Michael S.} and Junna Oba and Angeliki Pantazi and Michael Parfenov and Park, {Peter J.} and Parker, {Joel S.} and Alexander Penson and Perou, {Charles M.} and Todd Pihl and Robert Pilarski and Alexei Protopopov and Amie Radenbaugh and Karan Rai and Ramirez, {Nilsa C.} and Xiaojia Ren and Reynolds, {Sheila M.} and Jeffrey Roach and Robertson, {A. Gordon} and Sergio Roman-Roman and Jason Roszik and Sara Sadeghi and Gordon Saksena and Xavier Sastre and Dirk Schadendorf and Schein, {Jacqueline E.} and Lynn Schoenfield and Schumacher, {Steven E.} and Jonathan Seidman and Sahil Seth and Geetika Sethi and Margi Sheth and Yan Shi and Carol Shields and Juliann Shih and Ilya Shmulevich and Simons, {Janae V.} and Singh, {Arun D.} and Payal Sipahimalani and Tara Skelly and Heidi Sofia and Soloway, {Matthew G.} and Xingzhi Song and Stern, {Marc Henri} and Joshua Stuart and Qiang Sun and Huandong Sun and Angela Tam and Donghui Tan and Ming Tang and Jiabin Tang and Roy Tarnuzzer and Taylor, {Barry S.} and Nina Thiessen and Vesteinn Thorsson and Kane Tse and Vladislav Uzunangelov and Umadevi Veluvolu and Verhaak, {Roel G.W.} and Doug Voet and Vonn Walter and Yunhu Wan and Zhining Wang and Weinstein, {John N.} and Wilkerson, {Matthew D.} and Williams, {Michelle D.} and Lisa Wise and Woodman, {Scott E.} and Tina Wong and Ye Wu and Liming Yang and Lixing Yang and Christina Yau and Zenklusen, {Jean C.} and Jiashan Zhang and Hailei Zhang and Erik Zmuda and Cherniack, {Andrew D.} and Christopher Benz and Mills, {Gordon B.} and Verhaak, {Roel G.W.} and Griewank, {Klaus G.} and Ina Felau and Zenklusen, {Jean C.} and Gershenwald, {Jeffrey E.} and Lynn Schoenfield and Lazar, {Alexander J.} and Abdel-Rahman, {Mohamed H.} and Sergio Roman-Roman and Stern, {Marc Henri} and Cebulla, {Colleen M.} and Williams, {Michelle D.} and Jager, {Martine J.} and Coupland, {Sarah E.} and Bita Esmaeli and Cyriac Kandoth and Woodman, {Scott E.}",
year = "2017",
month = "8",
day = "14",
doi = "10.1016/j.ccell.2017.07.003",
language = "English (US)",
volume = "32",
pages = "204--220.e15",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",

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TY - JOUR

T1 - Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma

AU - Robertson, A. Gordon

AU - Shih, Juliann

AU - Yau, Christina

AU - Gibb, Ewan A.

AU - Oba, Junna

AU - Mungall, Karen L.

AU - Hess, Julian M.

AU - Uzunangelov, Vladislav

AU - Walter, Vonn

AU - Danilova, Ludmila

AU - Lichtenberg, Tara M.

AU - Kucherlapati, Melanie

AU - Kimes, Patrick K.

AU - Tang, Ming

AU - Penson, Alexander

AU - Babur, Ozgun

AU - Akbani, Rehan

AU - Bristow, Christopher A.

AU - Hoadley, Katherine A.

AU - Iype, Lisa

AU - Chang, Matthew T.

AU - Abdel-Rahman, Mohamed H.

AU - Akbani, Rehan

AU - Ally, Adrian

AU - Auman, J. Todd

AU - Babur, Ozgun

AU - Balasundaram, Miruna

AU - Balu, Saianand

AU - Benz, Christopher

AU - Beroukhim, Rameen

AU - Birol, Inanc

AU - Bodenheimer, Tom

AU - Bowen, Jay

AU - Bowlby, Reanne

AU - Bristow, Christopher A.

AU - Brooks, Denise

AU - Carlsen, Rebecca

AU - Cebulla, Colleen M.

AU - Chang, Matthew T.

AU - Cherniack, Andrew D.

AU - Chin, Lynda

AU - Cho, Juok

AU - Chuah, Eric

AU - Chudamani, Sudha

AU - Cibulskis, Carrie

AU - Cibulskis, Kristian

AU - Cope, Leslie

AU - Coupland, Sarah E.

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AU - Benz, Christopher

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AU - Woodman, Scott E.

PY - 2017/8/14

Y1 - 2017/8/14

N2 - 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.

AB - 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.

KW - EIF1AX

KW - GNA11

KW - GNAQ

KW - molecular subtypes

KW - monosomy 3

KW - noncoding RNA

KW - SF3B1

KW - SRSF2

KW - TCGA

KW - uveal melanoma

UR - http://www.scopus.com/inward/record.url?scp=85026887361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026887361&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2017.07.003

DO - 10.1016/j.ccell.2017.07.003

M3 - Article

C2 - 28810145

AN - SCOPUS:85026887361

VL - 32

SP - 204-220.e15

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 2

ER -