Next-Generation Sequencing for Patients with Sarcoma: A Single Center Experience.

Area of Science:

• Oncology
• Genomics
• Molecular Pathology

Background:

• Sarcomas are a diverse group of over 50 mesenchymal cancers with largely unknown driver mutations.
• Current treatments for metastatic sarcoma include chemotherapy and non-specific kinase inhibitors.
• The utility of next-generation sequencing (NGS) in sarcoma clinical practice is not yet established.

Purpose of the Study:

• To evaluate the utility of a targeted next-generation sequencing (NGS) platform in identifying actionable mutations in sarcoma patients.
• To assess the potential of NGS to guide patients towards mutation-specific clinical trials.

Main Methods:

• Retrospective analysis of 133 sarcoma tumor samples using a targeted NGS platform.
• The NGS panel covered over 400 cancer-related genes (405 DNA, 265 RNA).

Main Results:

• An average of two gene alterations were detected per sample, with 88% of samples harboring at least one mutation.
• Common mutations were found in cell cycle genes (TP53, CDKN2A/B, RB1) and the PI3-kinase pathway (PTEN, PIK3Ca).
• Seventy-five mutations (40% of patients) were targetable with existing drugs, enabling clinical trial enrollment.

Conclusions:

• Targeted NGS readily detects mutations in sarcoma patients.
• Approximately 40% of patients had mutations actionable by existing drugs within clinical trials.
• Targeted NGS is a valuable tool for directing sarcoma patients to relevant clinical trials.