Oncotarget | Analysis of mutations in primary and metastatic synovial sarcoma

The cover for issue 96 of Oncotarget features Figure 5, "Analysis of the effects of metastatic synovial sarcoma-associated ADAM17 mutations using cell migration assay," by Xing, et al.

To explore the possibilities to investigate metastatic mechanisms of synovial sarcoma, the research team 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, they examined the effect of the multiple missense mutations of ADAM17, which were identified solely in metastatic synovial sarcoma.

Therefore, like ADAM17-P729H, other mutations they 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.

Figure 5: Analysis of the effects of metastatic synovial sarcoma-associated ADAM17 mutations using cell migration assay. The graph represents the percentage of cells migrated after 17 h. All the cells carrying the SS18-SSX1 fusion gene in addition to expressing the wild-type ADAM17, ADAM17-P729H, or ADAM17-K805T. All the results were are expressed as the means ± standard errors from three independent experiments. ^*P < 0.05.

Dr. Y. Eugene Yu from the 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 and the Genetics, Genomics and Bioinformatics Program, State University of New York at Buffalo, Buffalo, NY, USA "Synovial sarcoma is a highly aggressive and distinct soft tissue sarcoma and the most common non-rhabdomyosarcoma soft tissue sarcoma in childhood and adolescence."

"Synovial sarcoma is a highly aggressive and distinct soft tissue sarcoma and the most common non-rhabdomyosarcoma soft tissue sarcoma in childhood and adolescence."

- Dr. Y. Eugene Yu, Children's Guild Foundation Down Syndrome Research Program, Genetics and Genomics Program, Department of Cancer Genetics and Genomics, Roswell Park Cancer Institute

Histological subtypes of SS include biphasic tumors containing epithelia-like/spindle cells, monophasic tumors containing only spindle cells, and poorly differentiated tumors.

In short, the prognosis of metastatic SS remains dismal and the vast majority of mortality is the result of metastatic disease and not the local recurrence.

Such efforts have identified differential mutational profiles between primary and metastatic tumors for lung cancer, breast cancer, hepatocellular carcinoma, colorectal cancer, and non-melanoma skin cancer, laying the ground for uncovering potential biomarkers and drivers for tumor progression and metastasis.

In the present study, they extended this effort to SS for the first time and revealed the novel mutations on the affected genes detected solely in metastatic SS.

The Yu research team concluded, in their Oncotarget Research Paper, "Metastatic SS remains a major challenge, and thus identification of metastatic drivers of this tumor type and unraveling of the associated metastatic mechanisms remain an urgent task."

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DOI - https://doi.org/10.18632/oncotarget.26416

Full text - https://doi.org/10.18632/oncotarget.26416

Correspondence to - Y. Eugene Yu - yuejin.yu@roswellpark.org

Keywords - synovial sarcoma, SS18-SSX, metastasis, whole exome sequencing, ADAM 17

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