Abstract 290: Development and characterization of antibodies specific for the SS18-SSX fusion protein in synovial sarcoma

Synovial sarcoma (SS) is a soft tissue cancer characterized by the fusion of the SS18 gene, which encodes for a subunit of the BAF ATP-dependent chromatin remodeling complex, with either SSX1, SSX2, or SSX4 genes. The resulting SS18-SSX fusion protein is incorporated into the BAF complex, where it evicts wild-type SMARCB1 (BAF47) and retargets the complex to polycomb-repressed chromatin domains, thus activating oncogenic gene expression to drive tumor progression. Traditional means of diagnosis of SS include immunohistochemical staining, including that for the biomarker TLE1, but TLE1 is not overexpressed in all tumors and cases ultimately need to be confirmed by either FISH or PCR assays to detect the SS18-SSX fusion. We have developed the first highly specific, recombinant monoclonal antibodies for the detection of SS18-SSX fusion proteins by immunohistochemistry and for the capture of SS18-SSX-containing BAF complexes in cells, with downstream utility in biochemistry and genomics-centered approaches such as ChIP-seq. The E9 × 9V clone directly targets the highly conserved fusion breakpoint, while the E5A2C clone detects the C-terminus of the SSX protein family and is capable of recognizing alternative breakpoints. Taken together, our data show that these antibodies can accurately and reproducibly detect the SS18-SSX fusion protein in SS cells and tissues. Citation Format: Curtis Desilets, Fang Chen, Christopher Comeau, Katrina Costa, Katherine Crosby, Michelle Ferrante, Christopher Grange, Maggie Patrikas, Matthew McBride, Esther Baranov, Jason Hornick, Cigall Kadoch. Development and characterization of antibodies specific for the SS18-SSX fusion protein in synovial sarcoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 290.