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Integrated Molecular Characterization of Uterine Carcinosarcoma

Cancer Cell. Volume 31 Issue 3: p411-423, 13 March 2017 10.1016/j.ccell.2017.02.010

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 amongst 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.

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