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; Cancer Genome Atlas Research Network; John N Weinstein; Jiashan Zhang; Rehan Akbani; Douglas A Levine

doi:10.1016/j.ccell.2017.02.010

Integrated Molecular Characterization of Uterine Carcinosarcoma

Cancer Cell. 2017 Mar 13;31(3):411-423. doi: 10.1016/j.ccell.2017.02.010.

Authors

Andrew D Cherniack¹, Hui Shen², Vonn Walter³, Chip Stewart¹, Bradley A Murray¹, Reanne Bowlby⁴, Xin Hu⁵, Shiyun Ling⁵, Robert A Soslow⁶, Russell R Broaddus⁵, Rosemary E Zuna⁷, Gordon Robertson⁴, Peter W Laird², Raju Kucherlapati⁸, Gordon B Mills⁵; Cancer Genome Atlas Research Network; John N Weinstein⁵, Jiashan Zhang⁹, Rehan Akbani¹⁰, Douglas A Levine¹¹

Collaborators

Cancer Genome Atlas Research Network:
Rehan Akbani, Adrian Ally, J Todd Auman, Miruna Balasundaram, Saianand Balu, Stephen 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

Affiliations

¹ The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
² Van Andel Research Institute, Center for Epigenetics, Grand Rapids, MI 49503, USA.
³ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
⁵ The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁶ Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁷ Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
⁸ Harvard Medical School, Boston, MA 02115, USA.
⁹ National Cancer Institute, Bethesda, MD 20892, USA.
¹⁰ The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: rakbani@mdanderson.org.
¹¹ Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: douglas.levine@nyumc.org.

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.

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

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Carcinosarcoma / genetics*
Carcinosarcoma / pathology
DNA Copy Number Variations
Epithelial-Mesenchymal Transition
Female
Humans
Mutation
Uterine Neoplasms / genetics*
Uterine Neoplasms / pathology

Abstract

Publication types

MeSH terms

Grants and funding