Identification of a Novel FUS/ETV4 Fusion and Comparative Analysis with Other Ewing Sarcoma Fusion Proteins.

Autor:	Boone MA; Biomedical Sciences Graduate Program, College of Medicine, The Ohio State University, Columbus, Ohio.; Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio., Taslim C; Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio., Crow JC; Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio., Selich-Anderson J; Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio., Watson M; LabPLUS, Auckland City Hospital, Grafton, Auckland, New Zealand., Heppner P; Starship Children's Hospital, Grafton, Auckland, New Zealand., Hamill J; Starship Children's Hospital, Grafton, Auckland, New Zealand., Wood AC; Starship Children's Hospital, Grafton, Auckland, New Zealand.; University of Auckland, Private Bag, Auckland, New Zealand., Lessnick SL; Biomedical Sciences Graduate Program, College of Medicine, The Ohio State University, Columbus, Ohio. stephen.lessnick@nationwidechildrens.org.; Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio.; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, Ohio., Winstanley M; Starship Children's Hospital, Grafton, Auckland, New Zealand.; University of Auckland, Private Bag, Auckland, New Zealand.
Jazyk:	angličtina
Zdroj:	Molecular cancer research : MCR [Mol Cancer Res] 2021 Nov; Vol. 19 (11), pp. 1795-1801. Date of Electronic Publication: 2021 Aug 31.
DOI:	10.1158/1541-7786.MCR-21-0354
Abstrakt:	Ewing sarcoma is a pediatric bone cancer defined by a chromosomal translocation fusing one of the FET family members to an ETS transcription factor. There have been seven reported chromosomal translocations, with the most recent reported over a decade ago. We now report a novel FET/ETS translocation involving FUS and ETV4 detected in a patient with Ewing sarcoma. Here, we characterized FUS/ETV4 by performing genomic localization and transcriptional regulatory studies on numerous FET/ETS fusions in a Ewing sarcoma cellular model. Through this comparative analysis, we demonstrate significant similarities across these fusions, and in doing so, validate FUS/ETV4 as a bona fide Ewing sarcoma translocation. This study presents the first genomic comparison of Ewing sarcoma-associated translocations and reveals that the FET/ETS fusions share highly similar, but not identical, genomic localization and transcriptional regulation patterns. These data strengthen the notion that FET/ETS fusions are key drivers of, and thus pathognomonic for, Ewing sarcoma. IMPLICATIONS: Identification and initial characterization of the novel Ewing sarcoma fusion, FUS/ETV4, expands the family of Ewing fusions and extends the diagnostic possibilities for this aggressive tumor of adolescents and young adults. (©2021 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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