RNA-based fusion NGS panel testing for the improved classification of soft tissue sarcomas: A retrospective analysis.

Abstract

11541 Background: Accurate diagnosis of soft tissue sarcomas (STS) is critical for effective clinical management. The integration of genetic data enables precise tumor categorization, enhancing diagnostic accuracy. Methods: This study presents retrospective molecular classification data of 295 soft tissue sarcoma patients tested using a 110-gene Soft Tissue Sarcoma NGS panel developed at MedGenome Labs, Bangalore, India. The panel facilitates the simultaneous analysis of single nucleotide variants (SNVs), copy number variations, and RNA fusions in a single run. Results: Among the 295 cases, clinically relevant fusion or mutation was identified in 186 patients which led to the clarification or reassignment of diagnosis 45/186 (24%) of patients. Key reclassifications included 7 BCOR -rearranged sarcomas misdiagnosed as other sarcoma types histologically, 5 EWSR1::FLI1 cases accurately identified as Ewing’s sarcoma, and a myxoid liposarcoma case reclassified as Ewing-like sarcoma based on EWSR1::TFCP2 fusion. Additional findings included two HEY1::NCOA2 fusion cases reclassified as mesenchymal chondrosarcoma and a TAF15::NR4A3 fusion case revised to extraskeletal myxoid chondrosarcoma from synovial sarcoma. Likewise, few other diagnosis revisions are highlighted in the table below. Conclusions: These results emphasize the diagnostic utility of broad-panel NGS testing with RNA-based fusion detection, underscoring its significant impact on the accurate classification and improved clinical management of STS patients. Few STS types reclassified based on molecular findings. Histologic Subtype (number of cases) Molecular classification Molecular event Spindle Cell Sarcoma (1) Dermatofibrosarcoma protuberans COL1A1::PDGFB Synovial Sarcoma (1) Endometrial Stromal sarcoma ZC3H7B::BCOR Spindle Cell Sarcoma (1) Inflammatory Myofibroblastic Tumor CLTC::ALK Sarcomatoid carcinoma (1) Low grade fibromyxoid sarcoma FUS::TFCP2 Angiosarcoma (1); Sarcomatoid Carcinoma (1); Undifferentiated Sarcoma (1) Mucoepidermoid Carcinoma; Mucoepidermoid Carcinoma; Mucoepidermoid Carcinoma NUDT4::MAML2; NR1D1::MAML2; NR1D1::MAML2 Spindle Cell Sarcoma (1) Nodular Fascitis CALD1::USP6 Low grade fibromyxoid sarcoma? Synovial sarcoma? (1); Osteosarcoma (1); Rhabdomyosarcoma (1) Sclerosing Epithelioid Fibrosarcoma; Sclerosing Epithelioid Fibrosarcoma FUS::CREB3L1; EWSR1::CREB3L3; FUS::TFCP2 High grade sarcoma with hemangiopericytomatous pattern (1); Spindle Cell Sarcoma (1) Synovial Sarcoma; Synovial Sarcoma SS18::SSX1; SS18::SSX1 Epithelioid sarcoma (1); Inflammatory Myofibroblastic Tumor (1) Uncommon EWSR1 rearranged sarcoma; Uncommon EWSR1 rearranged sarcoma EWSR1::ZBTB44; ZC3H7B::EWSR1 Fibrosarcoma (1) Undifferentiated Mesenchymal tumours YAP1::KMT2A