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Ewing Sarcoma Cells Secrete EWS/Fli-1 Fusion mRNA via Microvesicles
Authors:Masanori Tsugita  Nami Yamada  Shunsuke Noguchi  Kazunari Yamada  Hiroshi Moritake  Katsuji Shimizu  Yukihiro Akao  Takatoshi Ohno
Affiliation:1. Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, Gifu, Japan.; 2. United Graduate School of Drug Discovery and Medical Information Sciences, Gifu, Gifu, Japan.; 3. United Graduate School of Veterinary Sciences, Gifu University, Gifu, Gifu, Japan.; 4. Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Miyazaki, Japan.; University Hospital of Modena and Reggio Emilia, Italy,
Abstract:Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant neoplasms that most often affect children and young adults in the first 2 decades of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24; 12), is detected in 95% of ES patients. Recently, it was validated that cells emit a heterogeneous mixture of vesicular, organelle-like structures (microvesicles, MVs) into their surroundings including blood and body fluids, and that these MVs contain a selected set of tumor-related proteins and high levels of mRNAs and miRNAs. In this present study, we detected the Ewing sarcoma-specific EWS/Fli-1 mRNA in MVs from the culture medium of ES cell lines carrying t(11;22) (q24; 12). Also, we detected this fusion gene in approximately 40% of the blood samples from mice inoculated with xenografts of TC135 or A673 cells. These findings indicate the EWS/Fli-1 mRNA in MVs might be a new non-invasive diagnostic marker for specific cases of Ewing sarcoma.
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