Transforming routine solid tumor profiling with automated next-generation sequencing: experience from a reference...

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Targeted therapies require comprehensive tumor molecular profiling.
• Integrated DNA- and RNA-based next-generation sequencing (NGS) offers a holistic approach to tumor characterization.
• Identifying actionable mutations is crucial for guiding personalized treatment strategies.

Purpose of the Study:

• To evaluate the utility of an integrated DNA-RNA NGS strategy for rapid therapeutic decision-making in diverse solid tumors.
• To assess the performance of an automated NGS platform in profiling lung adenocarcinoma, cholangiocarcinoma, and glioblastoma.
• To identify clinically relevant molecular alterations and co-mutations for personalized therapy.

Main Methods:

• Analysis of 546 tumor samples (lung adenocarcinoma, cholangiocarcinoma, glioblastoma) using an automated, in-house DNA-RNA NGS platform.
• Simultaneous detection of point mutations, gene fusions, copy number variants, and other alterations.
• Evaluation of sequencing success rates and turnaround time from sample collection to report delivery.

Main Results:

• High sequencing success rates (98.7%-100%) with a median 8-day turnaround time.
• Identification of frequent actionable mutations in lung adenocarcinoma (EGFR, KRAS) and associations with EGFR amplification.
• Consistent mutation profiles in cholangiocarcinoma and glioblastoma, validating the assay's robustness.
• Detection of actionable co-mutations (e.g., EGFR/KRAS with TP53) with potential therapeutic implications.

Conclusions:

• Integrated DNA-RNA NGS enables timely and precise molecular profiling of solid tumors.
• This comprehensive approach supports rapid therapeutic decisions and personalized medicine.
• The validated NGS platform is effective for detecting clinically significant alterations across various cancer types.