Integrated genomic characterization of endometrial carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-05-01

AUTHORS

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, Li Ding, Elaine R. Mardis, 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, Gad Getz, Wendy Winckler, Rameen Beroukhim, Stacey B. Gabriel, 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, Dong Zeng, 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, Yan Shi, 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 Jr, David J. Van Den Berg, Daniel J. Weisenberger, Peter W. Laird, Hui Shen, Lynda Chin, Jianhua Zhang, Gad Getz, Juok Cho, Daniel DiCara, Scott Frazer, David Heiman, Rui Jing, Pei Lin, Will Mallard, Petar Stojanov, Doug Voet, Hailei Zhang, Lihua Zou, Michael Noble, Mike Lawrence, 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, Douglas A. Levine, 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, Russell Broaddus, Paul J. Goodfellow, David Mutch, Nikolaus Schultz, Yuexin Liu, Rehan Akbani, Andrew D. Cherniack, Ethan Cerami, Nils Weinhold, Hui Shen, Katherine A. Hoadley, Ari B. Kahn, Daphne W. Bell, Pamela M. Pollock, Chen Wang, David A.Wheeler, Eve Shinbrot, Beth Y. Karlan, Andrew Berchuck, Sean C. Dowdy, Boris Winterhoff, Marc T. Goodman, A. Gordon Robertson, Rameen Beroukhim, Itai Pashtan, Helga B. Salvesen, Peter W. Laird, Michael Noble, Joshua Stuart, Li Ding, Cyriac Kandoth, C. Blake Gilks, Robert A. Soslow, Paul J. Goodfellow, David Mutch, Russell Broaddus, Wei Zhang, Gordon B. Mills, Raju Kucherlapati, Elaine R. Mardis, Douglas A. Levine, Brenda Ayala, Anna L. Chu, Mark A. Jensen, Prachi Kothiyal, Todd D. Pihl, Joan Pontius, David A. Pot, Eric E. Snyder, Deepak Srinivasan, Ari B. Kahn, Kenna R. Mills Shaw, Margi Sheth, Tanja Davidsen, Greg Eley Martin L. Ferguson, John A. Demchok, Liming Yang, Mark S. Guyer, Bradley A. Ozenberger, Heidi J. Sofia, Cyriac Kandoth, Nikolaus Schultz, Andrew D. Cherniack, Rehan Akbani, Yuexin Liu, Hui Shen, A. Gordon Robertson, Itai Pashtan, Ronglai Shen, Christopher C. Benz, Christina Yau, Peter W. Laird, Li Ding, Wei Zhang, Gordon B. Mills, Raju Kucherlapati, Elaine R. Mardis, Douglas A. Levine

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. More... »

PAGES

67

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature12113

DOI

http://dx.doi.org/10.1038/nature12113

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004984574

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23636398


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