Multiscale-omic assessment of EWSR1-NFATc2 fusion positive sarcomas identifies the mTOR pathway as a potential therapeutic target.

Autor:	Seligson ND; Department of Pharmacotherapy and Translational Research, The University of Florida, Jacksonville, FL, USA.; Department of Pharmacogenomics and Translational Research, Nemours Children's Specialty Care, Jacksonville, FL, USA.; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Nemours Children's Specialty Care, Jacksonville, FL, USA., Maradiaga RD; The Ohio State University Wexner Medical Center and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA., Stets CM; The Ohio State University Wexner Medical Center and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA., Katzenstein HM; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Nemours Children's Specialty Care, Jacksonville, FL, USA., Millis SZ; Foundation Medicine Inc, Cambridge, USA., Rogers A; Department of Radiology, The Ohio State University, Columbus, OH, USA., Hays JL; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH, USA., Chen JL; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. James.Chen@osumc.edu.; Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA. James.Chen@osumc.edu.
Jazyk:	angličtina
Zdroj:	NPJ precision oncology [NPJ Precis Oncol] 2021 May 21; Vol. 5 (1), pp. 43. Date of Electronic Publication: 2021 May 21.
DOI:	10.1038/s41698-021-00177-0
Abstrakt:	Sarcomas harboring EWSR1-NFATc2 fusions have historically been categorized and treated as Ewing sarcoma. Emerging evidence suggests unique molecular characteristics and chemotherapy sensitivities in EWSR1-NFATc2 fusion positive sarcomas. Comprehensive genomic profiles of 1024 EWSR1 fusion positive sarcomas, including 14 EWSR1-NFATc2 fusions, were identified in the FoundationCore® database. Additional data from the Gene Expression Omnibus, the Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas datasets were included for analysis. EWSR1-NFATc2 fusion positive sarcomas were genomically distinct from traditional Ewing sarcoma and demonstrated upregulation of the mTOR pathway. We also present a case of a 58-year-old male patient with metastatic EWSR1-NFATc2 fusion positive sarcoma who achieved 47 months of disease stabilization when treated with combination mTOR and VEGF inhibition. EWSR1-NFATc2 fusion positive sarcomas are molecularly distinct entities with overactive mTOR signaling; which may be therapeutically targetable. These findings support the use of precision medicine in the Ewing family of tumors.
Databáze:	MEDLINE
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