Detection of Gene Fusions in Soft Tissue Sarcoma Using Next-Generation Sequencing

Area of Science:

• Oncology
• Genomics
• Molecular Pathology

Background:

• Soft tissue sarcomas (STS) present significant molecular heterogeneity.
• Recurrent gene fusions are crucial for STS diagnosis and targeted therapy, but their clinical impact needs further elucidation.

Purpose of the Study:

• To investigate the utility of next-generation sequencing (NGS) for detecting gene fusions in STS.
• To explore the clinical implications of identified gene fusions in patients receiving neoadjuvant chemoradiotherapy.

Main Methods:

• NGS (FusionPlex Sarcoma v2) and bioinformatic analysis were performed on FFPE core needle biopsy specimens.
• The study included patients from a phase II clinical trial receiving neoadjuvant chemoradiotherapy (UNRESARC protocol).

Main Results:

• Gene fusions were detected in 3 of 9 patients (33%), exclusively in high-grade (G3) tumors.
• Identified fusions included SGSH-PRKCA, LINC01133-OGA, and JAZF1-MYH7B with a concurrent PRKCA rearrangement.
• Fusion-positive cases exhibited stable radiological disease and moderate pathological response, while fusion-negative cases showed varied outcomes.

Conclusions:

• Broad genomic profiling can offer valuable molecular insights in challenging STS cases.
• In this series, detected gene fusions did not alter systemic treatment or demonstrate prognostic/predictive value.