Integrated Molecular Characterization of Uterine Carcinosarcoma

Publication date: 13 March 2017
Source:Cancer Cell, Volume 31, Issue 3
Author(s): 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, John N. Weinstein, Jiashan Zhang, Rehan Akbani, Douglas A. Levine
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.

Teaser

Cherniack et al. perform integrated molecular analyses of uterine carcinosarcomas and identify alterations in canonical pathways containing therapeutic targets currently in clinical trials. They also dissect the interaction between genomic and epigenomic regulations of epithelial-to-mesenchymal transition.


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