title: Integrated Molecular Characterization of Uterine Carcinosarcoma.
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.
authors.affiliation: The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cherniack
authors.affiliation: Van Andel Research Institute, Center for Epigenetics, Grand Rapids, MI 49503, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Vonn
authors.initials: V
authors.lastname: Walter
authors.affiliation: The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
authors.forename: Chip
authors.initials: C
authors.lastname: Stewart
authors.affiliation: The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Murray
authors.affiliation: Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors.forename: Reanne
authors.initials: R
authors.lastname: Bowlby
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Ling
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Broaddus
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Zuna
authors.affiliation: Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Robertson
authors.affiliation: Van Andel Research Institute, Center for Epigenetics, Grand Rapids, MI 49503, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Raju
authors.initials: R
authors.lastname: Kucherlapati
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Weinstein
authors.affiliation: National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Jiashan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: rakbani@mdanderson.org.
authors.forename: Rehan
authors.initials: R
authors.lastname: Akbani
authors.affiliation: Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: douglas.levine@nyumc.org.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
mesh_terms: D002296:Carcinosarcoma / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D009154:Mutation; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
keywords: EMT; TGGA; The Cancer Genome Atlas; UCS; endometrial cancer; epithelial-to-mesenchymal transition; gynecologic cancer; gynecologic oncology; translational science; uterine carcinosarcoma