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

Integrated Molecular Characterization of Uterine Carcinosarcoma.

Collaborators (146)

Akbani R, Ally A, Auman JT, Balasundaram M, Balu S, Baylin SB, Beroukhim R, Bodenheimer T, Bogomolniy F, Boice L, Bootwalla MS, Bowen J, Bowlby R, Broaddus R, Brooks D, Carlsen R, Cherniack AD, Cho J, Chuah E, Chudamani S, Cibulskis K, Cline M, Dao F, David M, Demchok JA, Dhalla N, Dowdy S, Felau I, Ferguson ML, Frazer S, Frick J, Gabriel S, Gastier-Foster JM, Gehlenborg N, Gerken M, Getz G, Gupta M, Haussler D, Hayes DN, Heiman DI, Hess J, Hoadley KA, Hoffmann R, Holt RA, Hoyle AP, Hu X, Huang M, Hutter CM, Jefferys SR, Jones SJM, Jones CD, Kanchi RS, Kandoth C, Kasaian K, Kerr S, Kim J, Lai PH, Laird PW, Lander E, Lawrence MS, Lee D, Leraas KM, Leshchiner I, Levine DA, Lichtenberg TM, Lin P, Ling S, Liu J, Liu W, Liu Y, Lolla L, Lu Y, Ma Y, Maglinte DT, Marra MA, Mayo M, Meng S, Meyerson M, Mieczkowski PA, Mills GB, Moore RA, Mose LE, Mungall AJ, Mungall K, Murray BA, Naresh R, Noble MS, Olvera N, Parker JS, Perou CM, Perou AH, Pihl T, Radenbaugh AJ, Ramirez NC, Rathmell WK, Roach J, Robertson AG, Sadeghi S, Saksena G, Salvesen HB, Schein JE, Schumacher SE, Shen H, Sheth M, Shi Y, Shih J, Simons JV, Sipahimalani P, Skelly T, Sofia HJ, Soloway MG, Soslow RA, Sougnez C, Stewart C, Sun C, Tam A, Tan D, Tarnuzzer R, Thiessen N, Thorne LB, Tse K, Tseng J, Van Den Berg DJ, Veluvolu U, Verhaak RGW, Voet D, von Bismarck A, Walter V, Wan Y, Wang Z, Wang C, Weinstein JN, Weisenberger DJ, Wilkerson MD, Winterhoff B, Wise L, Wong T, Wu Y, Yang L, Zenklusen JC, Zhang JJ, Zhang H, Zhang W, Zhu JC, Zmuda E, Zuna RE.

Author information

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

PMID:
28292439
PMCID:
PMC5599133
DOI:
10.1016/j.ccell.2017.02.010
[Indexed for MEDLINE]
Free PMC Article

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