Molecular Characterization of Soft Tissue Sarcomas Using RNA-Based Next-Generation Sequencing.

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Soft tissue sarcomas (STS) present diagnostic and therapeutic challenges.
• Current methods like histopathology and immunohistochemistry lack molecular detail.
• Understanding STS molecular complexity is crucial for improved patient outcomes.

Purpose of the Study:

• To assess RNA-based next-generation sequencing (RNA-NGS) for molecular characterization of STS.
• To identify transcriptomic mechanisms associated with STS aggressiveness and treatment resistance.
• To explore the utility of RNA-NGS in precision medicine for STS.

Main Methods:

• Analysis of RNA from 24 STS patient samples using a targeted pan-cancer panel.
• Sequencing performed on the Illumina platform with bioinformatic analysis (DRAGEN, DESeq2).
• Comparison with adipose and skeletal muscle tissue controls.

Main Results:

• RNA-NGS identified single-nucleotide polymorphisms and differential gene expression in STS.
• Overexpression of proliferation (e.g., TOP2A, MKI67), ECM (e.g., COL11A1), and developmental genes (e.g., HOXD13) was observed.
• Distinct transcriptomic profiles were found in leiomyosarcoma, with clinically relevant gene fusions detected.

Conclusions:

• RNA-NGS provides significant biological and clinical insights into the molecular landscape of STS.
• This technology can help elucidate mechanisms of tumor aggressiveness and treatment resistance.
• RNA-NGS supports integration into precision medicine workflows for STS diagnosis and management.