Then and Now: Decoding the Chromatin Machinery Behind Synovial Sarcoma

A new profile by Mariella Bodemeier Loayza Careaga, PhD, published in The Scientist, revisits biochemist Cigall Kadoch’s research nearly a decade after the publication first covered her work, tracing how her lab has continued to map the molecular hijacking that drives synovial sarcoma.

The BAF Complex and the SS18-SSX Fusion

Kadoch’s research centers on BAF complexes, large protein machines that control gene expression by regulating chromatin accessibility. These complexes are mutated in over 20% of all human cancers. In synovial sarcoma, a translocation of just 78 amino acids fuses the BAF subunit SS18 with a protein called SSX. This SS18-SSX fusion oncoprotein hijacks the BAF complex, expelling the normal SS18 protein and a tumor suppressor subunit, causing the chromatin remodeler to malfunction and drive disease.

New Findings

Using synovial sarcoma cell lines and patient samples, Kadoch’s team discovered that SS18-SSX-containing BAF complexes target genes normally silenced by polycomb repressive complexes (PRCs), evicting these repressors and switching on genes that should stay off. “That really established this cancer-specific hijacking of the BAF complex,” Kadoch said. Her team further found that the fusion’s 78-amino-acid tail directs the complex to a specific chemical mark on nucleosomes placed by PRCs, revealing why the complex lands where it does. A second mechanism, direct binding between BAF subunits and highly expressed transcription factors, also helps determine genomic targeting.

Why This Matters for the SS Community

These findings pinpoint exactly where and why the SS18-SSX-driven BAF complex acts in synovial sarcoma, offering specific molecular interactions that could be targeted with precision therapies rather than broader, less selective approaches. The work has also extended to other cancers, including lung and endometrial cancer, suggesting findings rooted in synovial sarcoma research may have wider therapeutic reach. Kadoch has helped translate this science toward the clinic through Foghorn Therapeutics, a biotech company she co-founded that targets components of the chromatin regulatory system in BAF-associated cancers.

For more information, read theoriginal article here. For more information about the Synovial Sarcoma Foundation, please visit our website.