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• W2904291804 abstract "// Zhuo Xing 1, * , Lei Wei 2, * , Xiaoling Jiang 1, * , Jeffrey Conroy 3, 4 , Sean Glenn 3, 4 , Wiam Bshara 5 , Tao Yu 1, 6 , Annie Pao 1 , Shinya Tanaka 7 , Akira Kawai 8 , Christopher Choi 9 , Jianmin Wang 2 , Song Liu 2, # , Carl Morrison 3, 4, 5, # and Y. Eugene Yu 1, 10, # 1 The Children's Guild Foundation Down Syndrome Research Program, Genetics and Genomics Program, Department of Cancer Genetics and Genomics, Roswell Park Cancer Institute, Buffalo, NY, USA 2 Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA 3 Center for Personalized Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA 4 OmniSeq Inc., Buffalo, NY, USA 5 Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA 6 Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China 7 Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan 8 Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan 9 Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA 10 Genetics, Genomics and Bioinformatics Program, State University of New York at Buffalo, Buffalo, NY, USA * First three authors should be regarded as joint first authors # Last three authors contributed equally to this paper Correspondence to: Y. Eugene Yu, email: yuejin.yu@roswellpark.org Keywords: synovial sarcoma; SS18-SSX; metastasis; whole exome sequencing; ADAM 17 Received: October 11, 2018      Accepted: November 16, 2018      Published: December 07, 2018 ABSTRACT Synovial sarcoma is the most common pediatric non-rhabdomyosarcoma soft tissue sarcoma and accounts for about 8–10% of all soft tissue sarcoma in childhood and adolescence. The presence of a chromosomal translocation-associated SS18-SSX -fusion gene is causally linked to development of primary synovial sarcoma. Metastases occur in approximately 50–70% of synovial sarcoma cases with yet unknown mechanisms, which led to about 70–80% mortality rate in five years. To explore the possibilities to investigate metastatic mechanisms of synovial sarcoma, we carried out the first genome-wide search for potential genetic biomarkers and drivers associated with metastasis by comparative mutational profiling of 18 synovial sarcoma samples isolated from four patients carrying the primary tumors and another four patients carrying the metastatic tumors through whole exome sequencing. Selected from the candidates yielded from this effort, we examined the effect of the multiple missense mutations of ADAM17, which were identified solely in metastatic synovial sarcoma. The mutant alleles as well as the wild-type control were expressed in the mammalian cells harboring the SS18 - SSX1 fusion gene. The ADAM17-P729H mutation was shown to enhance cell migration, a phenotype associated with metastasis. Therefore, like ADAM17-P729H, other mutations we identified solely in metastatic synovial sarcoma may also have the potential to serve as an entry point for unraveling the metastatic mechanisms of synovial sarcoma." @default.
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• W2904291804 date "2018-12-07" @default.
• W2904291804 modified "2023-09-27" @default.
• W2904291804 title "Analysis of mutations in primary and metastatic synovial sarcoma" @default.
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• W2904291804 doi "https://doi.org/10.18632/oncotarget.26416" @default.
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