Integrated Molecular Characterization of Uterine Carcinosarcoma

Andrew D. Cherniack, Hui Shen, Vonn Walter, Chip Stewart, Bradley A. Murray, Reanne Bowlby, Xin Hu, Shiyun Ling, Robert A. Soslow, Russell R. Broaddus, Rosemary E. Zuna, Gordon Robertson, Peter W. Laird, Raju Kucherlapati, Gordon B. Mills, Rehan Akbani, Adrian Ally, J. Todd Auman, Miruna Balasundaram, Saianand BaluStephen B. Baylin, Rameen Beroukhim, Tom Bodenheimer, Faina Bogomolniy, Lori Boice, Moiz S. Bootwalla, Jay Bowen, Reanne Bowlby, Russell Broaddus, Denise Brooks, Rebecca Carlsen, Andrew D. Cherniack, Juok Cho, Eric Chuah, Sudha Chudamani, Kristian Cibulskis, Melissa Cline, Fanny Dao, Mutch David, John A. Demchok, Noreen Dhalla, Sean Dowdy, Ina Felau, Martin L. Ferguson, Scott Frazer, Jessica Frick, Stacey Gabriel, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, Manaswi Gupta, David Haussler, D. Neil Hayes, David I. Heiman, Julian Hess, Katherine A. Hoadley, Robert Hoffmann, Robert A. Holt, Alan P. Hoyle, Xin Hu, Mei Huang, Carolyn M. Hutter, Stuart R. Jefferys, Steven J.M. Jones, Corbin D. Jones, Rupa S. Kanchi, Cyriac Kandoth, Katayoon Kasaian, Sarah Kerr, Jaegil Kim, Phillip H. Lai, Peter W. Laird, Eric Lander, Michael S. Lawrence, Darlene Lee, Kristen M. Leraas, Ignaty Leshchiner, Douglas A. Levine, Tara M. Lichtenberg, Pei Lin, Shiyun Ling, Jia Liu, Wenbin Liu, Yuexin Liu, Laxmi Lolla, Yiling Lu, Yussanne Ma, Dennis T. Maglinte, Marco A. Marra, Michael Mayo, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, Gordon B. Mills, Richard A. Moore, Lisle E. Mose, Andrew J. Mungall, Karen Mungall, Bradley A. Murray, Rashi Naresh, Michael S. Noble, Narciso Olvera, Joel S. Parker, Charles M. Perou, Amy H. Perou, Todd Pihl, Amie J. Radenbaugh, Nilsa C. Ramirez, W. Kimryn Rathmell, Jeffrey Roach, A. Gordon Robertson, Sara Sadeghi, Gordon Saksena, Helga B. Salvesen, Jacqueline E. Schein, Steven E. Schumacher, Hui Shen, Margi Sheth, Yan Shi, Juliann Shih, Janae V. Simons, Payal Sipahimalani, Tara Skelly, Heidi J. Sofia, Matthew G. Soloway, Robert A. Soslow, Carrie Sougnez, Chip Stewart, Charlie Sun, Angela Tam, Donghui Tan, Roy Tarnuzzer, Nina Thiessen, Leigh B. Thorne, Kane Tse, Jill Tseng, David J. Van Den Berg, Umadevi Veluvolu, Roel G.W. Verhaak, Doug Voet, Amanda von Bismarck, Vonn Walter, Yunhu Wan, Zhining Wang, Chen Wang, John N. Weinstein, Daniel J. Weisenberger, Matthew D. Wilkerson, Boris Winterhoff, Lisa Wise, Tina Wong, Ye Wu, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Hailei Zhang, Wei Zhang, Jing chun Zhu, Erik Zmuda, Rosemary E. Zuna, John N. Weinstein, Jiashan Zhang, Rehan Akbani, Douglas A. Levine

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.

Original languageEnglish (US)
Pages (from-to)411-423
Number of pages13
JournalCancer Cell
Volume31
Issue number3
DOIs
StatePublished - Mar 13 2017

Bibliographical note

Funding Information:
We wish to thank all patients and families who contributed to this study. This?work was supported by the following grants from the US NIH: U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672. Andrew D. Cherniack and Matthew Meyerson declare research funding from Bayer AG.

Keywords

  • EMT
  • TGGA
  • The Cancer Genome Atlas
  • UCS
  • endometrial cancer
  • epithelial-to-mesenchymal transition
  • gynecologic cancer
  • gynecologic oncology
  • translational science
  • uterine carcinosarcoma

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