Abstract A004-PR012: Investigating the potential of extracellular vesicle biomarkers for synovial sarcoma detection

Synovial sarcoma (SS) is a rare and aggressive soft tissue cancer with high heterogeneity, low 5- and 10-year survival rates, and a high risk for recurrence and metastasis. SS tumors are characterized by the t(X;18)(p11.2;q11.2) chromosomal translocation that results in a unique SS18:SSX gene fusion. Current diagnostic approaches include histology, PCR, and fluorescent in situ hybridization (FISH), however these methods require surgically resected tumor samples. There are currently no viable options for non-invasive detection of SS, which contributes to delays in detecting advanced disease. Recent studies suggest that extracellular vesicles play important roles in various aspects of cancer biology and can be used as non-invasive biomarkers for diagnosis. We have performed bulk RNA sequencing (RNA-seq) of extracellular vesicular RNA (evRNA) and have confirmed that SS18:SSX fusion transcripts are packaged into extracellular vesicles (EVs) secreted by patient-derived SS cell lines. This project aims to develop a non-invasive liquid biopsy detection technique by applying emerging breakthrough technologies in nanopore-integrated optofluidic platforms. This system has been shown to provide a label-free and amplification-free single-molecule detection in the attomolar concentration range, which is commensurate with clinically-relevant biomarker concentrations (Sampad et al, 2024. PNAS). We anticipate that capturing the secreted SS18-SSX biomarker from SS-derived EVs via this system will provide a low complexity, highly sensitive, and clinically feasible method for SS diagnosis and disease monitoring, as well as provide a proof-of-concept method that we aim to expand in SS patient blood samples. Citation Format: Maryke Grobler, S M Saiduzzaman, Ruiting Xu, Yvonne Vasquez, Anouk van den Bout, Holly C. Beale, Ranxin Zhang, David Geller, Rui Yang, Bang Hoang, Holger Schmidt, Olena Vaske. Investigating the potential of extracellular vesicle biomarkers for synovial sarcoma detection [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2):Abstract nr A004-PR012.