Transcriptomic Profiling of Relapsed Rhabdomyosarcoma: Pre- and Post-Treatment Tissue Analysis Reveals Molecular...

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma.
• Molecular profiling has improved risk stratification, but the evolution of therapy resistance in RMS is poorly understood.
• This study investigates the molecular mechanisms of treatment failure in high-risk, relapsed RMS.

Purpose of the Study:

• To uncover insights into the biology of RMS treatment failure.
• To characterize the molecular evolution of relapsed RMS.
• To identify differential gene expression patterns associated with therapy resistance.

Main Methods:

• Transcriptomic profiling of formalin-fixed, paraffin-embedded (FFPE) tissue samples from 11 relapsed RMS patients.
• Matched samples from diagnosis and relapse were analyzed.
• High-throughput genomics (HTG) whole transcriptome panel was utilized.

Main Results:

• Eleven high-risk, relapsed RMS patients (5 fusion-positive, 6 fusion-negative) were analyzed.
• Myogenesis pathway and myogenic differentiation markers were enriched pre-treatment in fusion-positive RMS and post-treatment in fusion-negative RMS.
• Inflammatory response pathway enrichment was observed post-treatment in both fusion-positive and fusion-negative RMS.

Conclusions:

• Relapsed RMS exhibits a fusion status-dependent evolutionary trajectory.
• Differential expression of myogenesis and inflammatory pathways contributes to treatment resistance.
• Understanding these pathways can inform future therapeutic strategies for relapsed RMS.