Comprehensive molecular characterization of urothelial bladder carcinoma

John N. Weinstein, Rehan Akbani, Bradley M. Broom, Wenyi Wang, Roeland G W Verhaak, David McConkey, Seth Lerner, Margaret Morgan, Chad J. Creighton, Carolyn Smith, Andrew D. Cherniack, Jaegil Kim, Chandra Sekhar Pedamallu, Michael S. Noble, Hikmat A. Al-Ahmadie, Victor E. Reuter, Jonathan E. Rosenberg, Dean F.Bajorin, Bernard H. Bochner, David B. Solit & 273 others Theresa Koppie, Brian Robinson, Dmitry A. Gordenin, David Fargo, Leszek J. Klimczak, Steven A. Roberts, Jessie Au, Peter W. Laird, Toshinori Hinoue, Nikolaus Schultz, Ricardo Ramirez, Donna Hansel, Katherine A. Hoadley, William Y. Kim, Jeffrey S. Damrauer, Stephen B. Baylin, Andrew J. Mungall, A. Gordon Robertson, Andy Chu, David J. Kwiatkowski, Carrie Sougnez, Kristian Cibulskis, Lee Lichtenstein, Andrey Sivachenko, Chip Stewart, Michael S. Lawrence, Gad Getz, Eric Lander, Stacey B. Gabrie, Lawrence Donehower, Scott L. Carter, Gordon Saksena, Steven E. Schumacher, Samuel S. Freeman, Joonil Jung, Ami S. Bhatt, Trevor Pugh, Rameen Beroukhim, Matthew Meyerson, Adrian Ally, Miruna Balasundaram, Yaron S N Butterfield, Noreen Dhalla, Carrie Hirst, Robert A. Holt, Steven J M Jones, Darlene Lee, Haiyan I. Li, Marco A. Marra, Michael Mayo, Richard A. Moore, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Tina Wong, Natasja Wye, Reanne Bowlby, Eric Chuah, Ranabir Guin, Hui Shen, Moiz S. Bootwalla, Timothy Triche, Phillip H. Lai, David J. Van Den Berg, Daniel J. Weisenberger, Saianand Balu, Tom Bodenheimer, Alan P. Hoyle, Stuart R. Jefferys, Shaowu Meng, Lisle E. Mose, Janae V. Simons, Mathew G. Soloway, Junyuan Wu, Joel S. Parker, D. Neil Hayes, Jeffrey Roach, Elizabeth Buda, Corbin D. Jones, Piotr A. Mieczkowski, Donghui Tan, Umadevi Veluvolu, Scot Waring, J. Todd Auman, Charles M. Perou, Matthew D. Wilkerson, Netty Santoso, Michael Parfenov, Xiaojia Ren, Angeliki Pantazi, Angela Hadjipanayis, Jonathan Seidman, Raju Kucherlapati, Semin Lee, Lixing Yang, Peter J. Park, Andrew Wei Xu, Alexei Protopopov, Jianhua Zhang, Christopher Bristow, Harshad S. Mahadeshwar, Sahil Seth, Xingzhi Song, Jiabin Tang, Dong Zeng, Lynda Chin, Charles Guo, Tod D. Casasent, Wenbin Liu, Zhenlin Ju, Thomas Motter, Bo Peng, Michael Ryan, Xiaoping Su, Ji Yeon Yang, Philip L. Lorenzi, Hui Yao, Nianxiang Zhang, Jiexin Zhang, Gordon B. Mills, Juok Cho, Daniel DiCara, Scott Frazer, Nils Gehlenborg, David I. Heiman, Pei Lin, Yingchun Liu, Petar Stojanov, Doug Voet, Hailei Zhang, Lihua Zou, Brady Bernard, Dick Kreisberg, Sheila Reynolds, Hector Rovira, Ilya Shmulevich, Jianjiong Gao, Anders Jacobsen, B. Arman Aksoy, Yevgeniy Antipin, Giovanni Ciriello, Gideon Dresdner, Benjamin Gross, William Lee, Boris Reva, Ronglai Shen, Rileen Sinha, S. Onur Sumer, Nils Weinhold, Marc Ladanyi, Chris Sander, Christopher Benz, Daniel Carlin, David Haussler, Sam Ng, Evano Paull, Joshua Stuart, Jing Zhu, Yuexin Liu, Wei Zhang, Barry S. Taylor, Tara M. Lichtenberg, Erik Zmuda, Thomas Barr, Aaron D. Black, Myra George, Benjamin Hanf, Carmen Helsel, Cynthia McAllister, Nilsa C. Ramirez, Teresa R. Tabler, Stephanie Weaver, Lisa Wise, Jay Bowen, Julie M. Gastier-Foster, Weiguo Jian, Sebrina Tello, Michael Ittman, Patricia Castro, Whitney D. McClenden, Richard Gibbs, Charles Saller, Katherine Tarvin, Jennifer M. DiPiero, Jennifer Owens, Roni Bollag, Qiang Li, Paul Weinberger, Christine Czerwinski, Lori Huelsenbeck-Dill, Mary Iacocca, Nicholas Petrelli, Brenda Rabeno, Pat Swanson, Troy Shelton, Erin Curley, Johanna Gardner, David Mallery, Robert Penny, Nguyen Van Bang, Phan Thi Hanh, Bernard Kohl, Xuan Van Le, Bui Duc Phu, Richard Thorp, Nguyen Viet Tien, Le Quang Vinh, George Sandusky, Eric Burks, Kimberly Christ, Jason Gee, Antonia Holway, Alireza Moinzadeh, Andrea Sorcini, Travis Sullivan, Ilana R. Garcia-Grossman, Ashley M. Regazzi, Lori Boice, Wendy Kimryn Rathmell, Leigh Thorne, Sheldon Bastacky, Benjamin Davies, Rajiv Dhir, Jeffrey Gingrich, Ronald Hrebinko, Jodi Maranchie, Joel Nelson, Anil Parwani, Wiam Bshara, Carmelo Gaudioso, Carl Morrison, Vina Alexopoulou, John Bartlett, Jay Engel, Sugy Kodeeswaran, Tatjana Antic, Peter H. O'Donnell, Norm D. Smith, Gary D. Steinberg, Sophie Egea, Carmen Gomez-Fernandez, Lynn Herbert, Merce Jorda, Mark Soloway, Allison Beaver, Suzie Carter, Payal Kapur, Cheryl M Lewis, Yair Lotan, Jolanta Bondaruk, Bogdan Czerniak, Eila Skinner, Kenneth Aldape, Mark A. Jensen, Ari B. Kahn, Todd D. Pihl, David A. Pot, Deepak Srinivasan, Yunhu Wan, Martin L. Ferguson, Jean Claude Zenklusen, Tanja Davidsen, John A. Demchok, Kenna R Mills Shaw, Margi Sheth, Roy Tarnuzzer, Zhining Wang, Liming Yang, Carolyn Hutter, Bradley A. Ozenberger, Heidi J. Sofia, Greg Eley

Research output: Contribution to journalArticle

1351 Citations (Scopus)

Abstract

Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.

Original languageEnglish (US)
Pages (from-to)315-322
Number of pages8
JournalNature
Volume507
Issue number7492
DOIs
StatePublished - 2014

Fingerprint

Urinary Bladder
Carcinoma
Chromatin
RNA Sequence Analysis
Neoplasms
Genome
Virus Integration
Genes
Atlases
Protein Sequence Analysis
Gene Silencing
Regulator Genes
MicroRNAs
Phosphatidylinositol 3-Kinases
Cell Cycle
Phosphotransferases
Mutation
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Weinstein, J. N., Akbani, R., Broom, B. M., Wang, W., Verhaak, R. G. W., McConkey, D., ... Eley, G. (2014). Comprehensive molecular characterization of urothelial bladder carcinoma. Nature, 507(7492), 315-322. https://doi.org/10.1038/nature12965

Comprehensive molecular characterization of urothelial bladder carcinoma. / Weinstein, John N.; Akbani, Rehan; Broom, Bradley M.; Wang, Wenyi; Verhaak, Roeland G W; McConkey, David; Lerner, Seth; Morgan, Margaret; Creighton, Chad J.; Smith, Carolyn; Cherniack, Andrew D.; Kim, Jaegil; Pedamallu, Chandra Sekhar; Noble, Michael S.; Al-Ahmadie, Hikmat A.; Reuter, Victor E.; Rosenberg, Jonathan E.; F.Bajorin, Dean; Bochner, Bernard H.; Solit, David B.; Koppie, Theresa; Robinson, Brian; Gordenin, Dmitry A.; Fargo, David; Klimczak, Leszek J.; Roberts, Steven A.; Au, Jessie; Laird, Peter W.; Hinoue, Toshinori; Schultz, Nikolaus; Ramirez, Ricardo; Hansel, Donna; Hoadley, Katherine A.; Kim, William Y.; Damrauer, Jeffrey S.; Baylin, Stephen B.; Mungall, Andrew J.; Robertson, A. Gordon; Chu, Andy; Kwiatkowski, David J.; Sougnez, Carrie; Cibulskis, Kristian; Lichtenstein, Lee; Sivachenko, Andrey; Stewart, Chip; Lawrence, Michael S.; Getz, Gad; Lander, Eric; Gabrie, Stacey B.; Donehower, Lawrence; Carter, Scott L.; Saksena, Gordon; Schumacher, Steven E.; Freeman, Samuel S.; Jung, Joonil; Bhatt, Ami S.; Pugh, Trevor; Beroukhim, Rameen; Meyerson, Matthew; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S N; Dhalla, Noreen; Hirst, Carrie; Holt, Robert A.; Jones, Steven J M; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina; Wye, Natasja; Bowlby, Reanne; Chuah, Eric; Guin, Ranabir; Shen, Hui; Bootwalla, Moiz S.; Triche, Timothy; Lai, Phillip H.; Van Den Berg, David J.; Weisenberger, Daniel J.; Balu, Saianand; Bodenheimer, Tom; Hoyle, Alan P.; Jefferys, Stuart R.; Meng, Shaowu; Mose, Lisle E.; Simons, Janae V.; Soloway, Mathew G.; Wu, Junyuan; Parker, Joel S.; Hayes, D. Neil; Roach, Jeffrey; Buda, Elizabeth; Jones, Corbin D.; Mieczkowski, Piotr A.; Tan, Donghui; Veluvolu, Umadevi; Waring, Scot; Auman, J. Todd; Perou, Charles M.; Wilkerson, Matthew D.; Santoso, Netty; Parfenov, Michael; Ren, Xiaojia; Pantazi, Angeliki; Hadjipanayis, Angela; Seidman, Jonathan; Kucherlapati, Raju; Lee, Semin; Yang, Lixing; Park, Peter J.; Xu, Andrew Wei; Protopopov, Alexei; Zhang, Jianhua; Bristow, Christopher; Mahadeshwar, Harshad S.; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Zeng, Dong; Chin, Lynda; Guo, Charles; Casasent, Tod D.; Liu, Wenbin; Ju, Zhenlin; Motter, Thomas; Peng, Bo; Ryan, Michael; Su, Xiaoping; Yang, Ji Yeon; Lorenzi, Philip L.; Yao, Hui; Zhang, Nianxiang; Zhang, Jiexin; Mills, Gordon B.; Cho, Juok; DiCara, Daniel; Frazer, Scott; Gehlenborg, Nils; Heiman, David I.; Lin, Pei; Liu, Yingchun; Stojanov, Petar; Voet, Doug; Zhang, Hailei; Zou, Lihua; Bernard, Brady; Kreisberg, Dick; Reynolds, Sheila; Rovira, Hector; Shmulevich, Ilya; Gao, Jianjiong; Jacobsen, Anders; Aksoy, B. Arman; Antipin, Yevgeniy; Ciriello, Giovanni; Dresdner, Gideon; Gross, Benjamin; Lee, William; Reva, Boris; Shen, Ronglai; Sinha, Rileen; Sumer, S. Onur; Weinhold, Nils; Ladanyi, Marc; Sander, Chris; Benz, Christopher; Carlin, Daniel; Haussler, David; Ng, Sam; Paull, Evano; Stuart, Joshua; Zhu, Jing; Liu, Yuexin; Zhang, Wei; Taylor, Barry S.; Lichtenberg, Tara M.; Zmuda, Erik; Barr, Thomas; Black, Aaron D.; George, Myra; Hanf, Benjamin; Helsel, Carmen; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Weaver, Stephanie; Wise, Lisa; Bowen, Jay; Gastier-Foster, Julie M.; Jian, Weiguo; Tello, Sebrina; Ittman, Michael; Castro, Patricia; McClenden, Whitney D.; Gibbs, Richard; Saller, Charles; Tarvin, Katherine; DiPiero, Jennifer M.; Owens, Jennifer; Bollag, Roni; Li, Qiang; Weinberger, Paul; Czerwinski, Christine; Huelsenbeck-Dill, Lori; Iacocca, Mary; Petrelli, Nicholas; Rabeno, Brenda; Swanson, Pat; Shelton, Troy; Curley, Erin; Gardner, Johanna; Mallery, David; Penny, Robert; Van Bang, Nguyen; Hanh, Phan Thi; Kohl, Bernard; Van Le, Xuan; Phu, Bui Duc; Thorp, Richard; Tien, Nguyen Viet; Vinh, Le Quang; Sandusky, George; Burks, Eric; Christ, Kimberly; Gee, Jason; Holway, Antonia; Moinzadeh, Alireza; Sorcini, Andrea; Sullivan, Travis; Garcia-Grossman, Ilana R.; Regazzi, Ashley M.; Boice, Lori; Rathmell, Wendy Kimryn; Thorne, Leigh; Bastacky, Sheldon; Davies, Benjamin; Dhir, Rajiv; Gingrich, Jeffrey; Hrebinko, Ronald; Maranchie, Jodi; Nelson, Joel; Parwani, Anil; Bshara, Wiam; Gaudioso, Carmelo; Morrison, Carl; Alexopoulou, Vina; Bartlett, John; Engel, Jay; Kodeeswaran, Sugy; Antic, Tatjana; O'Donnell, Peter H.; Smith, Norm D.; Steinberg, Gary D.; Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn; Jorda, Merce; Soloway, Mark; Beaver, Allison; Carter, Suzie; Kapur, Payal; Lewis, Cheryl M; Lotan, Yair; Bondaruk, Jolanta; Czerniak, Bogdan; Skinner, Eila; Aldape, Kenneth; Jensen, Mark A.; Kahn, Ari B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Wan, Yunhu; Ferguson, Martin L.; Zenklusen, Jean Claude; Davidsen, Tanja; Demchok, John A.; Shaw, Kenna R Mills; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Hutter, Carolyn; Ozenberger, Bradley A.; Sofia, Heidi J.; Eley, Greg.

In: Nature, Vol. 507, No. 7492, 2014, p. 315-322.

Research output: Contribution to journalArticle

Weinstein, JN, Akbani, R, Broom, BM, Wang, W, Verhaak, RGW, McConkey, D, Lerner, S, Morgan, M, Creighton, CJ, Smith, C, Cherniack, AD, Kim, J, Pedamallu, CS, Noble, MS, Al-Ahmadie, HA, Reuter, VE, Rosenberg, JE, F.Bajorin, D, Bochner, BH, Solit, DB, Koppie, T, Robinson, B, Gordenin, DA, Fargo, D, Klimczak, LJ, Roberts, SA, Au, J, Laird, PW, Hinoue, T, Schultz, N, Ramirez, R, Hansel, D, Hoadley, KA, Kim, WY, Damrauer, JS, Baylin, SB, Mungall, AJ, Robertson, AG, Chu, A, Kwiatkowski, DJ, Sougnez, C, Cibulskis, K, Lichtenstein, L, Sivachenko, A, Stewart, C, Lawrence, MS, Getz, G, Lander, E, Gabrie, SB, Donehower, L, Carter, SL, Saksena, G, Schumacher, SE, Freeman, SS, Jung, J, Bhatt, AS, Pugh, T, Beroukhim, R, Meyerson, M, Ally, A, Balasundaram, M, Butterfield, YSN, Dhalla, N, Hirst, C, Holt, RA, Jones, SJM, Lee, D, Li, HI, Marra, MA, Mayo, M, Moore, RA, Schein, JE, Sipahimalani, P, Tam, A, Thiessen, N, Wong, T, Wye, N, Bowlby, R, Chuah, E, Guin, R, Shen, H, Bootwalla, MS, Triche, T, Lai, PH, Van Den Berg, DJ, Weisenberger, DJ, Balu, S, Bodenheimer, T, Hoyle, AP, Jefferys, SR, Meng, S, Mose, LE, Simons, JV, Soloway, MG, Wu, J, Parker, JS, Hayes, DN, Roach, J, Buda, E, Jones, CD, Mieczkowski, PA, Tan, D, Veluvolu, U, Waring, S, Auman, JT, Perou, CM, Wilkerson, MD, Santoso, N, Parfenov, M, Ren, X, Pantazi, A, Hadjipanayis, A, Seidman, J, Kucherlapati, R, Lee, S, Yang, L, Park, PJ, Xu, AW, Protopopov, A, Zhang, J, Bristow, C, Mahadeshwar, HS, Seth, S, Song, X, Tang, J, Zeng, D, Chin, L, Guo, C, Casasent, TD, Liu, W, Ju, Z, Motter, T, Peng, B, Ryan, M, Su, X, Yang, JY, Lorenzi, PL, Yao, H, Zhang, N, Zhang, J, Mills, GB, Cho, J, DiCara, D, Frazer, S, Gehlenborg, N, Heiman, DI, Lin, P, Liu, Y, Stojanov, P, Voet, D, Zhang, H, Zou, L, Bernard, B, Kreisberg, D, Reynolds, S, Rovira, H, Shmulevich, I, Gao, J, Jacobsen, A, Aksoy, BA, Antipin, Y, Ciriello, G, Dresdner, G, Gross, B, Lee, W, Reva, B, Shen, R, Sinha, R, Sumer, SO, Weinhold, N, Ladanyi, M, Sander, C, Benz, C, Carlin, D, Haussler, D, Ng, S, Paull, E, Stuart, J, Zhu, J, Liu, Y, Zhang, W, Taylor, BS, Lichtenberg, TM, Zmuda, E, Barr, T, Black, AD, George, M, Hanf, B, Helsel, C, McAllister, C, Ramirez, NC, Tabler, TR, Weaver, S, Wise, L, Bowen, J, Gastier-Foster, JM, Jian, W, Tello, S, Ittman, M, Castro, P, McClenden, WD, Gibbs, R, Saller, C, Tarvin, K, DiPiero, JM, Owens, J, Bollag, R, Li, Q, Weinberger, P, Czerwinski, C, Huelsenbeck-Dill, L, Iacocca, M, Petrelli, N, Rabeno, B, Swanson, P, Shelton, T, Curley, E, Gardner, J, Mallery, D, Penny, R, Van Bang, N, Hanh, PT, Kohl, B, Van Le, X, Phu, BD, Thorp, R, Tien, NV, Vinh, LQ, Sandusky, G, Burks, E, Christ, K, Gee, J, Holway, A, Moinzadeh, A, Sorcini, A, Sullivan, T, Garcia-Grossman, IR, Regazzi, AM, Boice, L, Rathmell, WK, Thorne, L, Bastacky, S, Davies, B, Dhir, R, Gingrich, J, Hrebinko, R, Maranchie, J, Nelson, J, Parwani, A, Bshara, W, Gaudioso, C, Morrison, C, Alexopoulou, V, Bartlett, J, Engel, J, Kodeeswaran, S, Antic, T, O'Donnell, PH, Smith, ND, Steinberg, GD, Egea, S, Gomez-Fernandez, C, Herbert, L, Jorda, M, Soloway, M, Beaver, A, Carter, S, Kapur, P, Lewis, CM, Lotan, Y, Bondaruk, J, Czerniak, B, Skinner, E, Aldape, K, Jensen, MA, Kahn, AB, Pihl, TD, Pot, DA, Srinivasan, D, Wan, Y, Ferguson, ML, Zenklusen, JC, Davidsen, T, Demchok, JA, Shaw, KRM, Sheth, M, Tarnuzzer, R, Wang, Z, Yang, L, Hutter, C, Ozenberger, BA, Sofia, HJ & Eley, G 2014, 'Comprehensive molecular characterization of urothelial bladder carcinoma', Nature, vol. 507, no. 7492, pp. 315-322. https://doi.org/10.1038/nature12965
Weinstein JN, Akbani R, Broom BM, Wang W, Verhaak RGW, McConkey D et al. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507(7492):315-322. https://doi.org/10.1038/nature12965
Weinstein, John N. ; Akbani, Rehan ; Broom, Bradley M. ; Wang, Wenyi ; Verhaak, Roeland G W ; McConkey, David ; Lerner, Seth ; Morgan, Margaret ; Creighton, Chad J. ; Smith, Carolyn ; Cherniack, Andrew D. ; Kim, Jaegil ; Pedamallu, Chandra Sekhar ; Noble, Michael S. ; Al-Ahmadie, Hikmat A. ; Reuter, Victor E. ; Rosenberg, Jonathan E. ; F.Bajorin, Dean ; Bochner, Bernard H. ; Solit, David B. ; Koppie, Theresa ; Robinson, Brian ; Gordenin, Dmitry A. ; Fargo, David ; Klimczak, Leszek J. ; Roberts, Steven A. ; Au, Jessie ; Laird, Peter W. ; Hinoue, Toshinori ; Schultz, Nikolaus ; Ramirez, Ricardo ; Hansel, Donna ; Hoadley, Katherine A. ; Kim, William Y. ; Damrauer, Jeffrey S. ; Baylin, Stephen B. ; Mungall, Andrew J. ; Robertson, A. Gordon ; Chu, Andy ; Kwiatkowski, David J. ; Sougnez, Carrie ; Cibulskis, Kristian ; Lichtenstein, Lee ; Sivachenko, Andrey ; Stewart, Chip ; Lawrence, Michael S. ; Getz, Gad ; Lander, Eric ; Gabrie, Stacey B. ; Donehower, Lawrence ; Carter, Scott L. ; Saksena, Gordon ; Schumacher, Steven E. ; Freeman, Samuel S. ; Jung, Joonil ; Bhatt, Ami S. ; Pugh, Trevor ; Beroukhim, Rameen ; Meyerson, Matthew ; Ally, Adrian ; Balasundaram, Miruna ; Butterfield, Yaron S N ; Dhalla, Noreen ; Hirst, Carrie ; Holt, Robert A. ; Jones, Steven J M ; Lee, Darlene ; Li, Haiyan I. ; Marra, Marco A. ; Mayo, Michael ; Moore, Richard A. ; Schein, Jacqueline E. ; Sipahimalani, Payal ; Tam, Angela ; Thiessen, Nina ; Wong, Tina ; Wye, Natasja ; Bowlby, Reanne ; Chuah, Eric ; Guin, Ranabir ; Shen, Hui ; Bootwalla, Moiz S. ; Triche, Timothy ; Lai, Phillip H. ; Van Den Berg, David J. ; Weisenberger, Daniel J. ; Balu, Saianand ; Bodenheimer, Tom ; Hoyle, Alan P. ; Jefferys, Stuart R. ; Meng, Shaowu ; Mose, Lisle E. ; Simons, Janae V. ; Soloway, Mathew G. ; Wu, Junyuan ; Parker, Joel S. ; Hayes, D. Neil ; Roach, Jeffrey ; Buda, Elizabeth ; Jones, Corbin D. ; Mieczkowski, Piotr A. ; Tan, Donghui ; Veluvolu, Umadevi ; Waring, Scot ; Auman, J. Todd ; Perou, Charles M. ; Wilkerson, Matthew D. ; Santoso, Netty ; Parfenov, Michael ; Ren, Xiaojia ; Pantazi, Angeliki ; Hadjipanayis, Angela ; Seidman, Jonathan ; Kucherlapati, Raju ; Lee, Semin ; Yang, Lixing ; Park, Peter J. ; Xu, Andrew Wei ; Protopopov, Alexei ; Zhang, Jianhua ; Bristow, Christopher ; Mahadeshwar, Harshad S. ; Seth, Sahil ; Song, Xingzhi ; Tang, Jiabin ; Zeng, Dong ; Chin, Lynda ; Guo, Charles ; Casasent, Tod D. ; Liu, Wenbin ; Ju, Zhenlin ; Motter, Thomas ; Peng, Bo ; Ryan, Michael ; Su, Xiaoping ; Yang, Ji Yeon ; Lorenzi, Philip L. ; Yao, Hui ; Zhang, Nianxiang ; Zhang, Jiexin ; Mills, Gordon B. ; Cho, Juok ; DiCara, Daniel ; Frazer, Scott ; Gehlenborg, Nils ; Heiman, David I. ; Lin, Pei ; Liu, Yingchun ; Stojanov, Petar ; Voet, Doug ; Zhang, Hailei ; Zou, Lihua ; Bernard, Brady ; Kreisberg, Dick ; Reynolds, Sheila ; Rovira, Hector ; Shmulevich, Ilya ; Gao, Jianjiong ; Jacobsen, Anders ; Aksoy, B. Arman ; Antipin, Yevgeniy ; Ciriello, Giovanni ; Dresdner, Gideon ; Gross, Benjamin ; Lee, William ; Reva, Boris ; Shen, Ronglai ; Sinha, Rileen ; Sumer, S. Onur ; Weinhold, Nils ; Ladanyi, Marc ; Sander, Chris ; Benz, Christopher ; Carlin, Daniel ; Haussler, David ; Ng, Sam ; Paull, Evano ; Stuart, Joshua ; Zhu, Jing ; Liu, Yuexin ; Zhang, Wei ; Taylor, Barry S. ; Lichtenberg, Tara M. ; Zmuda, Erik ; Barr, Thomas ; Black, Aaron D. ; George, Myra ; Hanf, Benjamin ; Helsel, Carmen ; McAllister, Cynthia ; Ramirez, Nilsa C. ; Tabler, Teresa R. ; Weaver, Stephanie ; Wise, Lisa ; Bowen, Jay ; Gastier-Foster, Julie M. ; Jian, Weiguo ; Tello, Sebrina ; Ittman, Michael ; Castro, Patricia ; McClenden, Whitney D. ; Gibbs, Richard ; Saller, Charles ; Tarvin, Katherine ; DiPiero, Jennifer M. ; Owens, Jennifer ; Bollag, Roni ; Li, Qiang ; Weinberger, Paul ; Czerwinski, Christine ; Huelsenbeck-Dill, Lori ; Iacocca, Mary ; Petrelli, Nicholas ; Rabeno, Brenda ; Swanson, Pat ; Shelton, Troy ; Curley, Erin ; Gardner, Johanna ; Mallery, David ; Penny, Robert ; Van Bang, Nguyen ; Hanh, Phan Thi ; Kohl, Bernard ; Van Le, Xuan ; Phu, Bui Duc ; Thorp, Richard ; Tien, Nguyen Viet ; Vinh, Le Quang ; Sandusky, George ; Burks, Eric ; Christ, Kimberly ; Gee, Jason ; Holway, Antonia ; Moinzadeh, Alireza ; Sorcini, Andrea ; Sullivan, Travis ; Garcia-Grossman, Ilana R. ; Regazzi, Ashley M. ; Boice, Lori ; Rathmell, Wendy Kimryn ; Thorne, Leigh ; Bastacky, Sheldon ; Davies, Benjamin ; Dhir, Rajiv ; Gingrich, Jeffrey ; Hrebinko, Ronald ; Maranchie, Jodi ; Nelson, Joel ; Parwani, Anil ; Bshara, Wiam ; Gaudioso, Carmelo ; Morrison, Carl ; Alexopoulou, Vina ; Bartlett, John ; Engel, Jay ; Kodeeswaran, Sugy ; Antic, Tatjana ; O'Donnell, Peter H. ; Smith, Norm D. ; Steinberg, Gary D. ; Egea, Sophie ; Gomez-Fernandez, Carmen ; Herbert, Lynn ; Jorda, Merce ; Soloway, Mark ; Beaver, Allison ; Carter, Suzie ; Kapur, Payal ; Lewis, Cheryl M ; Lotan, Yair ; Bondaruk, Jolanta ; Czerniak, Bogdan ; Skinner, Eila ; Aldape, Kenneth ; Jensen, Mark A. ; Kahn, Ari B. ; Pihl, Todd D. ; Pot, David A. ; Srinivasan, Deepak ; Wan, Yunhu ; Ferguson, Martin L. ; Zenklusen, Jean Claude ; Davidsen, Tanja ; Demchok, John A. ; Shaw, Kenna R Mills ; Sheth, Margi ; Tarnuzzer, Roy ; Wang, Zhining ; Yang, Liming ; Hutter, Carolyn ; Ozenberger, Bradley A. ; Sofia, Heidi J. ; Eley, Greg. / Comprehensive molecular characterization of urothelial bladder carcinoma. In: Nature. 2014 ; Vol. 507, No. 7492. pp. 315-322.
@article{1eff0cacfd604e3b948b536b6ae21e9e,
title = "Comprehensive molecular characterization of urothelial bladder carcinoma",
abstract = "Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69{\%} of the tumours, including 42{\%} with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45{\%} with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.",
author = "Weinstein, {John N.} and Rehan Akbani and Broom, {Bradley M.} and Wenyi Wang and Verhaak, {Roeland G W} and David McConkey and Seth Lerner and Margaret Morgan and Creighton, {Chad J.} and Carolyn Smith and Cherniack, {Andrew D.} and Jaegil Kim and Pedamallu, {Chandra Sekhar} and Noble, {Michael S.} and Al-Ahmadie, {Hikmat A.} and Reuter, {Victor E.} and Rosenberg, {Jonathan E.} and Dean F.Bajorin and Bochner, {Bernard H.} and Solit, {David B.} and Theresa Koppie and Brian Robinson and Gordenin, {Dmitry A.} and David Fargo and Klimczak, {Leszek J.} and Roberts, {Steven A.} and Jessie Au and Laird, {Peter W.} and Toshinori Hinoue and Nikolaus Schultz and Ricardo Ramirez and Donna Hansel and Hoadley, {Katherine A.} and Kim, {William Y.} and Damrauer, {Jeffrey S.} and Baylin, {Stephen B.} and Mungall, {Andrew J.} and Robertson, {A. Gordon} and Andy Chu and Kwiatkowski, {David J.} and Carrie Sougnez and Kristian Cibulskis and Lee Lichtenstein and Andrey Sivachenko and Chip Stewart and Lawrence, {Michael S.} and Gad Getz and Eric Lander and Gabrie, {Stacey B.} and Lawrence Donehower and Carter, {Scott L.} and Gordon Saksena and Schumacher, {Steven E.} and Freeman, {Samuel S.} and Joonil Jung and Bhatt, {Ami S.} and Trevor Pugh and Rameen Beroukhim and Matthew Meyerson and Adrian Ally and Miruna Balasundaram and Butterfield, {Yaron S N} and Noreen Dhalla and Carrie Hirst and Holt, {Robert A.} and Jones, {Steven J M} and Darlene Lee and Li, {Haiyan I.} and Marra, {Marco A.} and Michael Mayo and Moore, {Richard A.} and Schein, {Jacqueline E.} and Payal Sipahimalani and Angela Tam and Nina Thiessen and Tina Wong and Natasja Wye and Reanne Bowlby and Eric Chuah and Ranabir Guin and Hui Shen and Bootwalla, {Moiz S.} and Timothy Triche and Lai, {Phillip H.} and {Van Den Berg}, {David J.} and Weisenberger, {Daniel J.} and Saianand Balu and Tom Bodenheimer and Hoyle, {Alan P.} and Jefferys, {Stuart R.} and Shaowu Meng and Mose, {Lisle E.} and Simons, {Janae V.} and Soloway, {Mathew G.} and Junyuan Wu and Parker, {Joel S.} and Hayes, {D. Neil} and Jeffrey Roach and Elizabeth Buda and Jones, {Corbin D.} and Mieczkowski, {Piotr A.} and Donghui Tan and Umadevi Veluvolu and Scot Waring and Auman, {J. Todd} and Perou, {Charles M.} and Wilkerson, {Matthew D.} and Netty Santoso and Michael Parfenov and Xiaojia Ren and Angeliki Pantazi and Angela Hadjipanayis and Jonathan Seidman and Raju Kucherlapati and Semin Lee and Lixing Yang and Park, {Peter J.} and Xu, {Andrew Wei} and Alexei Protopopov and Jianhua Zhang and Christopher Bristow and Mahadeshwar, {Harshad S.} and Sahil Seth and Xingzhi Song and Jiabin Tang and Dong Zeng and Lynda Chin and Charles Guo and Casasent, {Tod D.} and Wenbin Liu and Zhenlin Ju and Thomas Motter and Bo Peng and Michael Ryan and Xiaoping Su and Yang, {Ji Yeon} and Lorenzi, {Philip L.} and Hui Yao and Nianxiang Zhang and Jiexin Zhang and Mills, {Gordon B.} and Juok Cho and Daniel DiCara and Scott Frazer and Nils Gehlenborg and Heiman, {David I.} and Pei Lin and Yingchun Liu and Petar Stojanov and Doug Voet and Hailei Zhang and Lihua Zou and Brady Bernard and Dick Kreisberg and Sheila Reynolds and Hector Rovira and Ilya Shmulevich and Jianjiong Gao and Anders Jacobsen and Aksoy, {B. Arman} and Yevgeniy Antipin and Giovanni Ciriello and Gideon Dresdner and Benjamin Gross and William Lee and Boris Reva and Ronglai Shen and Rileen Sinha and Sumer, {S. Onur} and Nils Weinhold and Marc Ladanyi and Chris Sander and Christopher Benz and Daniel Carlin and David Haussler and Sam Ng and Evano Paull and Joshua Stuart and Jing Zhu and Yuexin Liu and Wei Zhang and Taylor, {Barry S.} and Lichtenberg, {Tara M.} and Erik Zmuda and Thomas Barr and Black, {Aaron D.} and Myra George and Benjamin Hanf and Carmen Helsel and Cynthia McAllister and Ramirez, {Nilsa C.} and Tabler, {Teresa R.} and Stephanie Weaver and Lisa Wise and Jay Bowen and Gastier-Foster, {Julie M.} and Weiguo Jian and Sebrina Tello and Michael Ittman and Patricia Castro and McClenden, {Whitney D.} and Richard Gibbs and Charles Saller and Katherine Tarvin and DiPiero, {Jennifer M.} and Jennifer Owens and Roni Bollag and Qiang Li and Paul Weinberger and Christine Czerwinski and Lori Huelsenbeck-Dill and Mary Iacocca and Nicholas Petrelli and Brenda Rabeno and Pat Swanson and Troy Shelton and Erin Curley and Johanna Gardner and David Mallery and Robert Penny and {Van Bang}, Nguyen and Hanh, {Phan Thi} and Bernard Kohl and {Van Le}, Xuan and Phu, {Bui Duc} and Richard Thorp and Tien, {Nguyen Viet} and Vinh, {Le Quang} and George Sandusky and Eric Burks and Kimberly Christ and Jason Gee and Antonia Holway and Alireza Moinzadeh and Andrea Sorcini and Travis Sullivan and Garcia-Grossman, {Ilana R.} and Regazzi, {Ashley M.} and Lori Boice and Rathmell, {Wendy Kimryn} and Leigh Thorne and Sheldon Bastacky and Benjamin Davies and Rajiv Dhir and Jeffrey Gingrich and Ronald Hrebinko and Jodi Maranchie and Joel Nelson and Anil Parwani and Wiam Bshara and Carmelo Gaudioso and Carl Morrison and Vina Alexopoulou and John Bartlett and Jay Engel and Sugy Kodeeswaran and Tatjana Antic and O'Donnell, {Peter H.} and Smith, {Norm D.} and Steinberg, {Gary D.} and Sophie Egea and Carmen Gomez-Fernandez and Lynn Herbert and Merce Jorda and Mark Soloway and Allison Beaver and Suzie Carter and Payal Kapur and Lewis, {Cheryl M} and Yair Lotan and Jolanta Bondaruk and Bogdan Czerniak and Eila Skinner and Kenneth Aldape and Jensen, {Mark A.} and Kahn, {Ari B.} and Pihl, {Todd D.} and Pot, {David A.} and Deepak Srinivasan and Yunhu Wan and Ferguson, {Martin L.} and Zenklusen, {Jean Claude} and Tanja Davidsen and Demchok, {John A.} and Shaw, {Kenna R Mills} and Margi Sheth and Roy Tarnuzzer and Zhining Wang and Liming Yang and Carolyn Hutter and Ozenberger, {Bradley A.} and Sofia, {Heidi J.} and Greg Eley",
year = "2014",
doi = "10.1038/nature12965",
language = "English (US)",
volume = "507",
pages = "315--322",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7492",

}

TY - JOUR

T1 - Comprehensive molecular characterization of urothelial bladder carcinoma

AU - Weinstein, John N.

AU - Akbani, Rehan

AU - Broom, Bradley M.

AU - Wang, Wenyi

AU - Verhaak, Roeland G W

AU - McConkey, David

AU - Lerner, Seth

AU - Morgan, Margaret

AU - Creighton, Chad J.

AU - Smith, Carolyn

AU - Cherniack, Andrew D.

AU - Kim, Jaegil

AU - Pedamallu, Chandra Sekhar

AU - Noble, Michael S.

AU - Al-Ahmadie, Hikmat A.

AU - Reuter, Victor E.

AU - Rosenberg, Jonathan E.

AU - F.Bajorin, Dean

AU - Bochner, Bernard H.

AU - Solit, David B.

AU - Koppie, Theresa

AU - Robinson, Brian

AU - Gordenin, Dmitry A.

AU - Fargo, David

AU - Klimczak, Leszek J.

AU - Roberts, Steven A.

AU - Au, Jessie

AU - Laird, Peter W.

AU - Hinoue, Toshinori

AU - Schultz, Nikolaus

AU - Ramirez, Ricardo

AU - Hansel, Donna

AU - Hoadley, Katherine A.

AU - Kim, William Y.

AU - Damrauer, Jeffrey S.

AU - Baylin, Stephen B.

AU - Mungall, Andrew J.

AU - Robertson, A. Gordon

AU - Chu, Andy

AU - Kwiatkowski, David J.

AU - Sougnez, Carrie

AU - Cibulskis, Kristian

AU - Lichtenstein, Lee

AU - Sivachenko, Andrey

AU - Stewart, Chip

AU - Lawrence, Michael S.

AU - Getz, Gad

AU - Lander, Eric

AU - Gabrie, Stacey B.

AU - Donehower, Lawrence

AU - Carter, Scott L.

AU - Saksena, Gordon

AU - Schumacher, Steven E.

AU - Freeman, Samuel S.

AU - Jung, Joonil

AU - Bhatt, Ami S.

AU - Pugh, Trevor

AU - Beroukhim, Rameen

AU - Meyerson, Matthew

AU - Ally, Adrian

AU - Balasundaram, Miruna

AU - Butterfield, Yaron S N

AU - Dhalla, Noreen

AU - Hirst, Carrie

AU - Holt, Robert A.

AU - Jones, Steven J M

AU - Lee, Darlene

AU - Li, Haiyan I.

AU - Marra, Marco A.

AU - Mayo, Michael

AU - Moore, Richard A.

AU - Schein, Jacqueline E.

AU - Sipahimalani, Payal

AU - Tam, Angela

AU - Thiessen, Nina

AU - Wong, Tina

AU - Wye, Natasja

AU - Bowlby, Reanne

AU - Chuah, Eric

AU - Guin, Ranabir

AU - Shen, Hui

AU - Bootwalla, Moiz S.

AU - Triche, Timothy

AU - Lai, Phillip H.

AU - Van Den Berg, David J.

AU - Weisenberger, Daniel J.

AU - Balu, Saianand

AU - Bodenheimer, Tom

AU - Hoyle, Alan P.

AU - Jefferys, Stuart R.

AU - Meng, Shaowu

AU - Mose, Lisle E.

AU - Simons, Janae V.

AU - Soloway, Mathew G.

AU - Wu, Junyuan

AU - Parker, Joel S.

AU - Hayes, D. Neil

AU - Roach, Jeffrey

AU - Buda, Elizabeth

AU - Jones, Corbin D.

AU - Mieczkowski, Piotr A.

AU - Tan, Donghui

AU - Veluvolu, Umadevi

AU - Waring, Scot

AU - Auman, J. Todd

AU - Perou, Charles M.

AU - Wilkerson, Matthew D.

AU - Santoso, Netty

AU - Parfenov, Michael

AU - Ren, Xiaojia

AU - Pantazi, Angeliki

AU - Hadjipanayis, Angela

AU - Seidman, Jonathan

AU - Kucherlapati, Raju

AU - Lee, Semin

AU - Yang, Lixing

AU - Park, Peter J.

AU - Xu, Andrew Wei

AU - Protopopov, Alexei

AU - Zhang, Jianhua

AU - Bristow, Christopher

AU - Mahadeshwar, Harshad S.

AU - Seth, Sahil

AU - Song, Xingzhi

AU - Tang, Jiabin

AU - Zeng, Dong

AU - Chin, Lynda

AU - Guo, Charles

AU - Casasent, Tod D.

AU - Liu, Wenbin

AU - Ju, Zhenlin

AU - Motter, Thomas

AU - Peng, Bo

AU - Ryan, Michael

AU - Su, Xiaoping

AU - Yang, Ji Yeon

AU - Lorenzi, Philip L.

AU - Yao, Hui

AU - Zhang, Nianxiang

AU - Zhang, Jiexin

AU - Mills, Gordon B.

AU - Cho, Juok

AU - DiCara, Daniel

AU - Frazer, Scott

AU - Gehlenborg, Nils

AU - Heiman, David I.

AU - Lin, Pei

AU - Liu, Yingchun

AU - Stojanov, Petar

AU - Voet, Doug

AU - Zhang, Hailei

AU - Zou, Lihua

AU - Bernard, Brady

AU - Kreisberg, Dick

AU - Reynolds, Sheila

AU - Rovira, Hector

AU - Shmulevich, Ilya

AU - Gao, Jianjiong

AU - Jacobsen, Anders

AU - Aksoy, B. Arman

AU - Antipin, Yevgeniy

AU - Ciriello, Giovanni

AU - Dresdner, Gideon

AU - Gross, Benjamin

AU - Lee, William

AU - Reva, Boris

AU - Shen, Ronglai

AU - Sinha, Rileen

AU - Sumer, S. Onur

AU - Weinhold, Nils

AU - Ladanyi, Marc

AU - Sander, Chris

AU - Benz, Christopher

AU - Carlin, Daniel

AU - Haussler, David

AU - Ng, Sam

AU - Paull, Evano

AU - Stuart, Joshua

AU - Zhu, Jing

AU - Liu, Yuexin

AU - Zhang, Wei

AU - Taylor, Barry S.

AU - Lichtenberg, Tara M.

AU - Zmuda, Erik

AU - Barr, Thomas

AU - Black, Aaron D.

AU - George, Myra

AU - Hanf, Benjamin

AU - Helsel, Carmen

AU - McAllister, Cynthia

AU - Ramirez, Nilsa C.

AU - Tabler, Teresa R.

AU - Weaver, Stephanie

AU - Wise, Lisa

AU - Bowen, Jay

AU - Gastier-Foster, Julie M.

AU - Jian, Weiguo

AU - Tello, Sebrina

AU - Ittman, Michael

AU - Castro, Patricia

AU - McClenden, Whitney D.

AU - Gibbs, Richard

AU - Saller, Charles

AU - Tarvin, Katherine

AU - DiPiero, Jennifer M.

AU - Owens, Jennifer

AU - Bollag, Roni

AU - Li, Qiang

AU - Weinberger, Paul

AU - Czerwinski, Christine

AU - Huelsenbeck-Dill, Lori

AU - Iacocca, Mary

AU - Petrelli, Nicholas

AU - Rabeno, Brenda

AU - Swanson, Pat

AU - Shelton, Troy

AU - Curley, Erin

AU - Gardner, Johanna

AU - Mallery, David

AU - Penny, Robert

AU - Van Bang, Nguyen

AU - Hanh, Phan Thi

AU - Kohl, Bernard

AU - Van Le, Xuan

AU - Phu, Bui Duc

AU - Thorp, Richard

AU - Tien, Nguyen Viet

AU - Vinh, Le Quang

AU - Sandusky, George

AU - Burks, Eric

AU - Christ, Kimberly

AU - Gee, Jason

AU - Holway, Antonia

AU - Moinzadeh, Alireza

AU - Sorcini, Andrea

AU - Sullivan, Travis

AU - Garcia-Grossman, Ilana R.

AU - Regazzi, Ashley M.

AU - Boice, Lori

AU - Rathmell, Wendy Kimryn

AU - Thorne, Leigh

AU - Bastacky, Sheldon

AU - Davies, Benjamin

AU - Dhir, Rajiv

AU - Gingrich, Jeffrey

AU - Hrebinko, Ronald

AU - Maranchie, Jodi

AU - Nelson, Joel

AU - Parwani, Anil

AU - Bshara, Wiam

AU - Gaudioso, Carmelo

AU - Morrison, Carl

AU - Alexopoulou, Vina

AU - Bartlett, John

AU - Engel, Jay

AU - Kodeeswaran, Sugy

AU - Antic, Tatjana

AU - O'Donnell, Peter H.

AU - Smith, Norm D.

AU - Steinberg, Gary D.

AU - Egea, Sophie

AU - Gomez-Fernandez, Carmen

AU - Herbert, Lynn

AU - Jorda, Merce

AU - Soloway, Mark

AU - Beaver, Allison

AU - Carter, Suzie

AU - Kapur, Payal

AU - Lewis, Cheryl M

AU - Lotan, Yair

AU - Bondaruk, Jolanta

AU - Czerniak, Bogdan

AU - Skinner, Eila

AU - Aldape, Kenneth

AU - Jensen, Mark A.

AU - Kahn, Ari B.

AU - Pihl, Todd D.

AU - Pot, David A.

AU - Srinivasan, Deepak

AU - Wan, Yunhu

AU - Ferguson, Martin L.

AU - Zenklusen, Jean Claude

AU - Davidsen, Tanja

AU - Demchok, John A.

AU - Shaw, Kenna R Mills

AU - Sheth, Margi

AU - Tarnuzzer, Roy

AU - Wang, Zhining

AU - Yang, Liming

AU - Hutter, Carolyn

AU - Ozenberger, Bradley A.

AU - Sofia, Heidi J.

AU - Eley, Greg

PY - 2014

Y1 - 2014

N2 - Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.

AB - Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.

UR - http://www.scopus.com/inward/record.url?scp=84897022815&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897022815&partnerID=8YFLogxK

U2 - 10.1038/nature12965

DO - 10.1038/nature12965

M3 - Article

VL - 507

SP - 315

EP - 322

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7492

ER -