Integrated genomic characterization of endometrial carcinoma

Gad Getz; Stacey B. Gabriel; Kristian Cibulskis; Eric Lander; Andrey Sivachenko; Carrie Sougnez; Mike Lawrence; Cyriac Kandoth; David Dooling; Robert Fulton; Lucinda Fulton; Joelle Kalicki-Veizer; Michael D. McLellan; Michelle O'Laughlin; Heather Schmidt; Richard K. Wilson; Kai Ye; Ding Li; Adrian Ally; Miruna Balasundaram; Inanc Birol; Yaron S.N. Butterfield; Rebecca Carlsen; Candace Carter; Andy Chu; Eric Chuah; Hye Jung E. Chun; Noreen Dhalla; Ranabir Guin; Carrie Hirst; Robert A. Holt; Steven J.M. Jones; Darlene Lee; Haiyan I. Li; Marco A. Marra; Michael Mayo; Richard A. Moore; Andrew J. Mungall; Patrick Plettner; Jacqueline E. Schein; Payal Sipahimalani; Angela Tam; Richard J. Varhol; A. Gordon Robertson; Andrew D. Cherniack; Itai Pashtan; Gordon Saksena; Robert C. Onofrio; Steven E. Schumacher; Barbara Tabak; Scott L. Carter; Bryan Hernandez; Jeff Gentry; Helga B. Salvesen; Kristin Ardlie; Wendy Winckler; Rameen Beroukhim; Matthew Meyerson; Angela Hadjipanayis; Semin Lee; Harshad S. Mahadeshwar; Peter Park; Alexei Protopopov; Xiaojia Ren; Sahil Seth; Xingzhi Song; Jiabin Tang; Ruibin Xi; Lixing Yang; Zeng Dong; Raju Kucherlapati; Lynda Chin; Jianhua Zhang; J. Todd Auman; Saianand Balu; Tom Bodenheimer; Elizabeth Buda; D. Neil Hayes; Alan P. Hoyle; Stuart R. Jefferys; Corbin D. Jones; Shaowu Meng; Piotr A. Mieczkowski; Lisle E. Mose; Joel S. Parker; Charles M. Perou; Jeff Roach; Shi Yan; Janae V. Simons; Mathew G. Soloway; Donghui Tan; Michael D. Topal; Scot Waring; Junyuan Wu; Katherine A. Hoadley; Stephen B. Baylin; Moiz S. Bootwalla; Phillip H. Lai; Timothy J. Triche; David J. Van Den Berg; Daniel J. Weisenberger; Peter W. Laird; Hui Shen; Juok Cho; Daniel Dicara; Scott Frazer; David Heiman; Rui Jing; Pei Lin; Will Mallard; Petar Stojanov; Doug Voet; Hailei Zhang; Lihua Zou; Michael Noble; Sheila M. Reynolds; Ilya Shmulevich; B. Arman Aksoy; Yevgeniy Antipin; Giovanni Ciriello; Gideon Dresdner; Jianjiong Gao; Benjamin Gross; Anders Jacobsen; Marc Ladanyi; Boris Reva; Chris Sander; Rileen Sinha; S. Onur Sumer; Barry S. Taylor; Ethan Cerami; Nils Weinhold; Nikolaus Schultz; Ronglai Shen; Stephen Benz; Ted Goldstein; David Haussler; Sam Ng; Christopher Szeto; Joshua Stuart; Christopher C. Benz; Christina Yau; Wei Zhang; Matti Annala; Bradley M. Broom; Tod D. Casasent; Zhenlin Ju; Han Liang; Guoyan Liu; Yiling Lu; Anna K. Unruh; Chris Wakefield; John N. Weinstein; Nianxiang Zhang; Yuexin Liu; Russell Broaddus; Rehan Akbani; Gordon B. Mills; Christopher Adams; Thomas Barr; Aaron D. Black; Jay Bowen; John Deardurff; Jessica Frick; Julie M. Gastier-Foster; Thomas Grossman; Hollie A. Harper; Melissa Hart-Kothari; Carmen Helsel; Aaron Hobensack; Harkness Kuck; Kelley Kneile; Kristen M. Leraas; Tara M. Lichtenberg; Cynthia McAllister; Robert E. Pyatt; Nilsa C. Ramirez; Teresa R. Tabler; Nathan Vanhoose; Peter White; Lisa Wise; Erik Zmuda; Nandita Barnabas; Charlenia Berry-Green; Victoria Blanc; Lori Boice; Michael Button; Adam Farkas; Alex Green; Jean MacKenzie; Dana Nicholson; Steve E. Kalloger; C. Blake Gilks; Beth Y. Karlan; Jenny Lester; Sandra Orsulic; Mark Borowsky; Mark Cadungog; Christine Czerwinski; Lori Huelsenbeck-Dill; Mary Iacocca; Nicholas Petrelli; Brenda Rabeno; Gary Witkin; Elena Nemirovich-Danchenko; Olga Potapova; Daniil Rotin; Andrew Berchuck; Michael Birrer; Phillip Disaia; Laura Monovich; Erin Curley; Johanna Gardner; David Mallery; Robert Penny; Sean C. Dowdy; Boris Winterhoff; Linda Dao; Bobbie Gostout; Alexandra Meuter; Attila Teoman; Fanny Dao; Narciso Olvera; Faina Bogomolniy; Karuna Garg; Robert A. Soslow; Mikhail Abramov; John M.S. Bartlett; Sugy Kodeeswaran; Jeremy Parfitt; Fedor Moiseenko; Blaise A. Clarke; Marc T. Goodman; Michael E. Carney; Rayna K. Matsuno; Jennifer Fisher; Mei Huang; W. Kimryn Rathmell; Leigh Thorne; Linda Van Le; Rajiv Dhir; Robert Edwards; Esther Elishaev; Kristin Zorn; Paul J. Goodfellow; David Mutch; Ari B. Kahn; Daphne W. Bell; Pamela M. Pollock; Chen Wang; David Wheeler; Eve Shinbrot; A. Gordon Robertson; Li Ding; C. Blake Gilks; Elaine R. Mardis; Brenda Ayala; Anna L. Chu; Mark A. Jensen; Prachi Kothiyal; Todd D. Pihl; Joan Pontius; David A. Pot; Eric E. Snyder; Deepak Srinivasan; Kenna R. Mills Shaw; Margi Sheth; Tanja Davidsen; Greg Eley; Martin L. Ferguson; Liming Yang; Mark S. Guyer; Bradley A. Ozenberger; Heidi J. Sofia; A. Gordon Robertson; Douglas A. Levine

doi:10.1038/nature12113

Integrated genomic characterization of endometrial carcinoma

Gad Getz, Stacey B. Gabriel, Kristian Cibulskis, Eric Lander, Andrey Sivachenko, Carrie Sougnez, Mike Lawrence, Cyriac Kandoth, David Dooling, Robert Fulton, Lucinda Fulton, Joelle Kalicki-Veizer, Michael D. McLellan, Michelle O'Laughlin, Heather Schmidt, Richard K. Wilson, Kai Ye, Ding Li, Adrian Ally, Miruna BalasundaramInanc Birol, Yaron S.N. Butterfield, Rebecca Carlsen, Candace Carter, Andy Chu, Eric Chuah, Hye Jung E. Chun, Noreen Dhalla, Ranabir Guin, Carrie Hirst, Robert A. Holt, Steven J.M. Jones, Darlene Lee, Haiyan I. Li, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Patrick Plettner, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Richard J. Varhol, A. Gordon Robertson, Andrew D. Cherniack, Itai Pashtan, Gordon Saksena, Robert C. Onofrio, Steven E. Schumacher, Barbara Tabak, Scott L. Carter, Bryan Hernandez, Jeff Gentry, Helga B. Salvesen, Kristin Ardlie, Wendy Winckler, Rameen Beroukhim, Matthew Meyerson, Angela Hadjipanayis, Semin Lee, Harshad S. Mahadeshwar, Peter Park, Alexei Protopopov, Xiaojia Ren, Sahil Seth, Xingzhi Song, Jiabin Tang, Ruibin Xi, Lixing Yang, Zeng Dong, Raju Kucherlapati, Lynda Chin, Jianhua Zhang, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Elizabeth Buda, D. Neil Hayes, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Joel S. Parker, Charles M. Perou, Jeff Roach, Shi Yan, Janae V. Simons, Mathew G. Soloway, Donghui Tan, Michael D. Topal, Scot Waring, Junyuan Wu, Katherine A. Hoadley, Stephen B. Baylin, Moiz S. Bootwalla, Phillip H. Lai, Timothy J. Triche, David J. Van Den Berg, Daniel J. Weisenberger, Peter W. Laird, Hui Shen, Juok Cho, Daniel Dicara, Scott Frazer, David Heiman, Rui Jing, Pei Lin, Will Mallard, Petar Stojanov, Doug Voet, Hailei Zhang, Lihua Zou, Michael Noble, Sheila M. Reynolds, Ilya Shmulevich, B. Arman Aksoy, Yevgeniy Antipin, Giovanni Ciriello, Gideon Dresdner, Jianjiong Gao, Benjamin Gross, Anders Jacobsen, Marc Ladanyi, Boris Reva, Chris Sander, Rileen Sinha, S. Onur Sumer, Barry S. Taylor, Ethan Cerami, Nils Weinhold, Nikolaus Schultz, Ronglai Shen, Stephen Benz, Ted Goldstein, David Haussler, Sam Ng, Christopher Szeto, Joshua Stuart, Christopher C. Benz, Christina Yau, Wei Zhang, Matti Annala, Bradley M. Broom, Tod D. Casasent, Zhenlin Ju, Han Liang, Guoyan Liu, Yiling Lu, Anna K. Unruh, Chris Wakefield, John N. Weinstein, Nianxiang Zhang, Yuexin Liu, Russell Broaddus, Rehan Akbani, Gordon B. Mills, Christopher Adams, Thomas Barr, Aaron D. Black, Jay Bowen, John Deardurff, Jessica Frick, Julie M. Gastier-Foster, Thomas Grossman, Hollie A. Harper, Melissa Hart-Kothari, Carmen Helsel, Aaron Hobensack, Harkness Kuck, Kelley Kneile, Kristen M. Leraas, Tara M. Lichtenberg, Cynthia McAllister, Robert E. Pyatt, Nilsa C. Ramirez, Teresa R. Tabler, Nathan Vanhoose, Peter White, Lisa Wise, Erik Zmuda, Nandita Barnabas, Charlenia Berry-Green, Victoria Blanc, Lori Boice, Michael Button, Adam Farkas, Alex Green, Jean MacKenzie, Dana Nicholson, Steve E. Kalloger, C. Blake Gilks, Beth Y. Karlan, Jenny Lester, Sandra Orsulic, Mark Borowsky, Mark Cadungog, Christine Czerwinski, Lori Huelsenbeck-Dill, Mary Iacocca, Nicholas Petrelli, Brenda Rabeno, Gary Witkin, Elena Nemirovich-Danchenko, Olga Potapova, Daniil Rotin, Andrew Berchuck, Michael Birrer, Phillip Disaia, Laura Monovich, Erin Curley, Johanna Gardner, David Mallery, Robert Penny, Sean C. Dowdy, Boris Winterhoff, Linda Dao, Bobbie Gostout, Alexandra Meuter, Attila Teoman, Fanny Dao, Narciso Olvera, Faina Bogomolniy, Karuna Garg, Robert A. Soslow, Mikhail Abramov, John M.S. Bartlett, Sugy Kodeeswaran, Jeremy Parfitt, Fedor Moiseenko, Blaise A. Clarke, Marc T. Goodman, Michael E. Carney, Rayna K. Matsuno, Jennifer Fisher, Mei Huang, W. Kimryn Rathmell, Leigh Thorne, Linda Van Le, Rajiv Dhir, Robert Edwards, Esther Elishaev, Kristin Zorn, Paul J. Goodfellow, David Mutch, Ari B. Kahn, Daphne W. Bell, Pamela M. Pollock, Chen Wang, David Wheeler, Eve Shinbrot, A. Gordon Robertson, Li Ding, C. Blake Gilks, Elaine R. Mardis, Brenda Ayala, Anna L. Chu, Mark A. Jensen, Prachi Kothiyal, Todd D. Pihl, Joan Pontius, David A. Pot, Eric E. Snyder, Deepak Srinivasan, Kenna R. Mills Shaw, Margi Sheth, Tanja Davidsen, Greg Eley, Martin L. Ferguson, Liming Yang, Mark S. Guyer, Bradley A. Ozenberger, Heidi J. Sofia, A. Gordon Robertson, Douglas A. Levine

Research output: Contribution to journal › Article › peer-review

3861 Scopus citations

Abstract

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

Original language	English
Pages (from-to)	67-73
Number of pages	7
Journal	Nature
Volume	497
Issue number	7447
DOIs	https://doi.org/10.1038/nature12113
State	Published - 2013

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10.1038/nature12113

Cite this

Getz, G., Gabriel, S. B., Cibulskis, K., Lander, E., Sivachenko, A., Sougnez, C., Lawrence, M., Kandoth, C., Dooling, D., Fulton, R., Fulton, L., Kalicki-Veizer, J., McLellan, M. D., O'Laughlin, M., Schmidt, H., Wilson, R. K., Ye, K., Li, D., Ally, A., ... Levine, D. A. (2013). Integrated genomic characterization of endometrial carcinoma. Nature, 497(7447), 67-73. https://doi.org/10.1038/nature12113

@article{7f36a885caee43c58bab1bf49ba7e156,

title = "Integrated genomic characterization of endometrial carcinoma",

abstract = "We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.",

author = "Gad Getz and Gabriel, {Stacey B.} and Kristian Cibulskis and Eric Lander and Andrey Sivachenko and Carrie Sougnez and Mike Lawrence and Cyriac Kandoth and David Dooling and Robert Fulton and Lucinda Fulton and Joelle Kalicki-Veizer and McLellan, {Michael D.} and Michelle O'Laughlin and Heather Schmidt and Wilson, {Richard K.} and Kai Ye and Ding Li and Adrian Ally and Miruna Balasundaram and Inanc Birol and Butterfield, {Yaron S.N.} and Rebecca Carlsen and Candace Carter and Andy Chu and Eric Chuah and Chun, {Hye Jung E.} and Noreen Dhalla and Ranabir Guin 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 Mungall, {Andrew J.} and Patrick Plettner and Schein, {Jacqueline E.} and Payal Sipahimalani and Angela Tam and Varhol, {Richard J.} and {Gordon Robertson}, A. and Cherniack, {Andrew D.} and Itai Pashtan and Gordon Saksena and Onofrio, {Robert C.} and Schumacher, {Steven E.} and Barbara Tabak and Carter, {Scott L.} and Bryan Hernandez and Jeff Gentry and Salvesen, {Helga B.} and Kristin Ardlie and Wendy Winckler and Rameen Beroukhim and Matthew Meyerson and Angela Hadjipanayis and Semin Lee and Mahadeshwar, {Harshad S.} and Peter Park and Alexei Protopopov and Xiaojia Ren and Sahil Seth and Xingzhi Song and Jiabin Tang and Ruibin Xi and Lixing Yang and Zeng Dong and Raju Kucherlapati and Lynda Chin and Jianhua Zhang and {Todd Auman}, J. and Saianand Balu and Tom Bodenheimer and Elizabeth Buda and {Neil Hayes}, D. and Hoyle, {Alan P.} and Jefferys, {Stuart R.} and Jones, {Corbin D.} and Shaowu Meng and Mieczkowski, {Piotr A.} and Mose, {Lisle E.} and Parker, {Joel S.} and Perou, {Charles M.} and Jeff Roach and Shi Yan and Simons, {Janae V.} and Soloway, {Mathew G.} and Donghui Tan and Topal, {Michael D.} and Scot Waring and Junyuan Wu and Hoadley, {Katherine A.} and Baylin, {Stephen B.} and Bootwalla, {Moiz S.} and Lai, {Phillip H.} and Triche, {Timothy J.} and {Van Den Berg}, {David J.} and Weisenberger, {Daniel J.} and Laird, {Peter W.} and Hui Shen and Juok Cho and Daniel Dicara and Scott Frazer and David Heiman and Rui Jing and Pei Lin and Will Mallard and Petar Stojanov and Doug Voet and Hailei Zhang and Lihua Zou and Michael Noble and Reynolds, {Sheila M.} and Ilya Shmulevich and {Arman Aksoy}, B. and Yevgeniy Antipin and Giovanni Ciriello and Gideon Dresdner and Jianjiong Gao and Benjamin Gross and Anders Jacobsen and Marc Ladanyi and Boris Reva and Chris Sander and Rileen Sinha and {Onur Sumer}, S. and Taylor, {Barry S.} and Ethan Cerami and Nils Weinhold and Nikolaus Schultz and Ronglai Shen and Stephen Benz and Ted Goldstein and David Haussler and Sam Ng and Christopher Szeto and Joshua Stuart and Benz, {Christopher C.} and Christina Yau and Wei Zhang and Matti Annala and Broom, {Bradley M.} and Casasent, {Tod D.} and Zhenlin Ju and Han Liang and Guoyan Liu and Yiling Lu and Unruh, {Anna K.} and Chris Wakefield and Weinstein, {John N.} and Nianxiang Zhang and Yuexin Liu and Russell Broaddus and Rehan Akbani and Mills, {Gordon B.} and Christopher Adams and Thomas Barr and Black, {Aaron D.} and Jay Bowen and John Deardurff and Jessica Frick and Gastier-Foster, {Julie M.} and Thomas Grossman and Harper, {Hollie A.} and Melissa Hart-Kothari and Carmen Helsel and Aaron Hobensack and Harkness Kuck and Kelley Kneile and Leraas, {Kristen M.} and Lichtenberg, {Tara M.} and Cynthia McAllister and Pyatt, {Robert E.} and Ramirez, {Nilsa C.} and Tabler, {Teresa R.} and Nathan Vanhoose and Peter White and Lisa Wise and Erik Zmuda and Nandita Barnabas and Charlenia Berry-Green and Victoria Blanc and Lori Boice and Michael Button and Adam Farkas and Alex Green and Jean MacKenzie and Dana Nicholson and Kalloger, {Steve E.} and {Blake Gilks}, C. and Karlan, {Beth Y.} and Jenny Lester and Sandra Orsulic and Mark Borowsky and Mark Cadungog and Christine Czerwinski and Lori Huelsenbeck-Dill and Mary Iacocca and Nicholas Petrelli and Brenda Rabeno and Gary Witkin and Elena Nemirovich-Danchenko and Olga Potapova and Daniil Rotin and Andrew Berchuck and Michael Birrer and Phillip Disaia and Laura Monovich and Erin Curley and Johanna Gardner and David Mallery and Robert Penny and Dowdy, {Sean C.} and Boris Winterhoff and Linda Dao and Bobbie Gostout and Alexandra Meuter and Attila Teoman and Fanny Dao and Narciso Olvera and Faina Bogomolniy and Karuna Garg and Soslow, {Robert A.} and Mikhail Abramov and Bartlett, {John M.S.} and Sugy Kodeeswaran and Jeremy Parfitt and Fedor Moiseenko and Clarke, {Blaise A.} and Goodman, {Marc T.} and Carney, {Michael E.} and Matsuno, {Rayna K.} and Jennifer Fisher and Mei Huang and {Kimryn Rathmell}, W. and Leigh Thorne and {Van Le}, Linda and Rajiv Dhir and Robert Edwards and Esther Elishaev and Kristin Zorn and Goodfellow, {Paul J.} and David Mutch and Kahn, {Ari B.} and Bell, {Daphne W.} and Pollock, {Pamela M.} and Chen Wang and David Wheeler and Eve Shinbrot and {Gordon Robertson}, A. and Li Ding and {Blake Gilks}, C. and Mardis, {Elaine R.} and Brenda Ayala and Chu, {Anna L.} and Jensen, {Mark A.} and Prachi Kothiyal and Pihl, {Todd D.} and Joan Pontius and Pot, {David A.} and Snyder, {Eric E.} and Deepak Srinivasan and {Mills Shaw}, {Kenna R.} and Margi Sheth and Tanja Davidsen and Greg Eley and Ferguson, {Martin L.} and Liming Yang and Guyer, {Mark S.} and Ozenberger, {Bradley A.} and Sofia, {Heidi J.} and {Gordon Robertson}, A. and Levine, {Douglas A.}",

note = "Funding Information: Acknowledgements We wish to thank all patients and families who contributed to this study.WethankM.Shethand L.Lundfor administrativecoordinationofTCGAactivities, G. Monemvasitis for editing the manuscript, and C. Gunter for critical reading of the manuscript. This work was supported by the following grants from the US National Institutes of Health: 5U24CA143799-04, 5U24CA143835-04, 5U24CA143840-04, 5U24CA143843-04, 5U24CA143845-04, 5U24CA143848-04, 5U24CA143858-04, 5U24CA143866-04, 5U24CA143867-04, 5U24CA143882-04, 5U24CA143883-04, 5U24CA144025-04, U54HG003067-11, U54HG003079-10 and U54HG003273-10.",

year = "2013",

doi = "10.1038/nature12113",

language = "English",

volume = "497",

pages = "67--73",

journal = "Nature",

issn = "0028-0836",

number = "7447",

}

Getz, G, Gabriel, SB, Cibulskis, K, Lander, E, Sivachenko, A, Sougnez, C, Lawrence, M, Kandoth, C, Dooling, D, Fulton, R , Fulton, L, Kalicki-Veizer, J, McLellan, MD, O'Laughlin, M, Schmidt, H, Wilson, RK, Ye, K, Li, D, Ally, A, Balasundaram, M, Birol, I, Butterfield, YSN, Carlsen, R, Carter, C, Chu, A, Chuah, E, Chun, HJE, Dhalla, N, Guin, R, Hirst, C, Holt, RA, Jones, SJM, Lee, D, Li, HI, Marra, MA, Mayo, M, Moore, RA, Mungall, AJ, Plettner, P, Schein, JE, Sipahimalani, P, Tam, A, Varhol, RJ, Gordon Robertson, A, Cherniack, AD, Pashtan, I, Saksena, G, Onofrio, RC, Schumacher, SE, Tabak, B, Carter, SL, Hernandez, B, Gentry, J, Salvesen, HB, Ardlie, K, Winckler, W, Beroukhim, R, Meyerson, M, Hadjipanayis, A, Lee, S, Mahadeshwar, HS, Park, P, Protopopov, A, Ren, X, Seth, S, Song, X, Tang, J, Xi, R, Yang, L, Dong, Z, Kucherlapati, R, Chin, L, Zhang, J, Todd Auman, J, Balu, S, Bodenheimer, T, Buda, E, Neil Hayes, D, Hoyle, AP, Jefferys, SR, Jones, CD, Meng, S, Mieczkowski, PA, Mose, LE, Parker, JS, Perou, CM, Roach, J, Yan, S, Simons, JV, Soloway, MG, Tan, D, Topal, MD, Waring, S, Wu, J, Hoadley, KA, Baylin, SB, Bootwalla, MS, Lai, PH, Triche, TJ, Van Den Berg, DJ, Weisenberger, DJ, Laird, PW, Shen, H, Cho, J, Dicara, D, Frazer, S, Heiman, D, Jing, R, Lin, P, Mallard, W, Stojanov, P, Voet, D, Zhang, H, Zou, L, Noble, M, Reynolds, SM, Shmulevich, I, Arman Aksoy, B, Antipin, Y, Ciriello, G, Dresdner, G, Gao, J, Gross, B, Jacobsen, A, Ladanyi, M, Reva, B, Sander, C, Sinha, R, Onur Sumer, S, Taylor, BS, Cerami, E, Weinhold, N, Schultz, N, Shen, R, Benz, S, Goldstein, T, Haussler, D, Ng, S, Szeto, C, Stuart, J, Benz, CC, Yau, C, Zhang, W, Annala, M, Broom, BM, Casasent, TD, Ju, Z, Liang, H, Liu, G, Lu, Y, Unruh, AK, Wakefield, C, Weinstein, JN, Zhang, N, Liu, Y, Broaddus, R, Akbani, R, Mills, GB, Adams, C, Barr, T, Black, AD, Bowen, J, Deardurff, J, Frick, J, Gastier-Foster, JM, Grossman, T, Harper, HA, Hart-Kothari, M, Helsel, C, Hobensack, A, Kuck, H, Kneile, K, Leraas, KM, Lichtenberg, TM, McAllister, C, Pyatt, RE, Ramirez, NC, Tabler, TR, Vanhoose, N, White, P, Wise, L, Zmuda, E, Barnabas, N, Berry-Green, C, Blanc, V, Boice, L, Button, M, Farkas, A, Green, A, MacKenzie, J, Nicholson, D, Kalloger, SE, Blake Gilks, C, Karlan, BY, Lester, J, Orsulic, S, Borowsky, M, Cadungog, M, Czerwinski, C, Huelsenbeck-Dill, L, Iacocca, M, Petrelli, N, Rabeno, B, Witkin, G, Nemirovich-Danchenko, E, Potapova, O, Rotin, D, Berchuck, A, Birrer, M, Disaia, P, Monovich, L, Curley, E, Gardner, J, Mallery, D, Penny, R, Dowdy, SC, Winterhoff, B, Dao, L, Gostout, B, Meuter, A, Teoman, A, Dao, F, Olvera, N, Bogomolniy, F, Garg, K, Soslow, RA, Abramov, M, Bartlett, JMS, Kodeeswaran, S, Parfitt, J, Moiseenko, F, Clarke, BA, Goodman, MT, Carney, ME, Matsuno, RK, Fisher, J, Huang, M, Kimryn Rathmell, W, Thorne, L, Van Le, L, Dhir, R, Edwards, R, Elishaev, E, Zorn, K, Goodfellow, PJ, Mutch, D, Kahn, AB, Bell, DW, Pollock, PM, Wang, C, Wheeler, D, Shinbrot, E, Gordon Robertson, A, Ding, L, Blake Gilks, C, Mardis, ER, Ayala, B, Chu, AL, Jensen, MA, Kothiyal, P, Pihl, TD, Pontius, J, Pot, DA, Snyder, EE, Srinivasan, D, Mills Shaw, KR, Sheth, M, Davidsen, T, Eley, G, Ferguson, ML, Yang, L, Guyer, MS, Ozenberger, BA, Sofia, HJ, Gordon Robertson, A & Levine, DA 2013, 'Integrated genomic characterization of endometrial carcinoma', Nature, vol. 497, no. 7447, pp. 67-73. https://doi.org/10.1038/nature12113

TY - JOUR

T1 - Integrated genomic characterization of endometrial carcinoma

AU - Getz, Gad

AU - Gabriel, Stacey B.

AU - Cibulskis, Kristian

AU - Lander, Eric

AU - Sivachenko, Andrey

AU - Sougnez, Carrie

AU - Lawrence, Mike

AU - Kandoth, Cyriac

AU - Dooling, David

AU - Fulton, Robert

AU - Fulton, Lucinda

AU - Kalicki-Veizer, Joelle

AU - McLellan, Michael D.

AU - O'Laughlin, Michelle

AU - Schmidt, Heather

AU - Wilson, Richard K.

AU - Ye, Kai

AU - Li, Ding

AU - Ally, Adrian

AU - Balasundaram, Miruna

AU - Birol, Inanc

AU - Butterfield, Yaron S.N.

AU - Carlsen, Rebecca

AU - Carter, Candace

AU - Chu, Andy

AU - Chuah, Eric

AU - Chun, Hye Jung E.

AU - Dhalla, Noreen

AU - Guin, Ranabir

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 - Mungall, Andrew J.

AU - Plettner, Patrick

AU - Schein, Jacqueline E.

AU - Sipahimalani, Payal

AU - Tam, Angela

AU - Varhol, Richard J.

AU - Gordon Robertson, A.

AU - Cherniack, Andrew D.

AU - Pashtan, Itai

AU - Saksena, Gordon

AU - Onofrio, Robert C.

AU - Schumacher, Steven E.

AU - Tabak, Barbara

AU - Carter, Scott L.

AU - Hernandez, Bryan

AU - Gentry, Jeff

AU - Salvesen, Helga B.

AU - Ardlie, Kristin

AU - Winckler, Wendy

AU - Beroukhim, Rameen

AU - Meyerson, Matthew

AU - Hadjipanayis, Angela

AU - Lee, Semin

AU - Mahadeshwar, Harshad S.

AU - Park, Peter

AU - Protopopov, Alexei

AU - Ren, Xiaojia

AU - Seth, Sahil

AU - Song, Xingzhi

AU - Tang, Jiabin

AU - Xi, Ruibin

AU - Yang, Lixing

AU - Dong, Zeng

AU - Kucherlapati, Raju

AU - Chin, Lynda

AU - Zhang, Jianhua

AU - Todd Auman, J.

AU - Balu, Saianand

AU - Bodenheimer, Tom

AU - Buda, Elizabeth

AU - Neil Hayes, D.

AU - Hoyle, Alan P.

AU - Jefferys, Stuart R.

AU - Jones, Corbin D.

AU - Meng, Shaowu

AU - Mieczkowski, Piotr A.

AU - Mose, Lisle E.

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N1 - Funding Information: Acknowledgements We wish to thank all patients and families who contributed to this study.WethankM.Shethand L.Lundfor administrativecoordinationofTCGAactivities, G. Monemvasitis for editing the manuscript, and C. Gunter for critical reading of the manuscript. This work was supported by the following grants from the US National Institutes of Health: 5U24CA143799-04, 5U24CA143835-04, 5U24CA143840-04, 5U24CA143843-04, 5U24CA143845-04, 5U24CA143848-04, 5U24CA143858-04, 5U24CA143866-04, 5U24CA143867-04, 5U24CA143882-04, 5U24CA143883-04, 5U24CA144025-04, U54HG003067-11, U54HG003079-10 and U54HG003273-10.

PY - 2013

Y1 - 2013

N2 - We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

AB - We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

UR - http://www.scopus.com/inward/record.url?scp=84877254190&partnerID=8YFLogxK

U2 - 10.1038/nature12113

DO - 10.1038/nature12113

M3 - Article

C2 - 23636398

AN - SCOPUS:84877254190

SN - 0028-0836

VL - 497

SP - 67

EP - 73

JO - Nature

JF - Nature

IS - 7447

ER -

Integrated genomic characterization of endometrial carcinoma

Abstract

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