Feasibility and clinical utility of a pan-solid tumor targeted RNA fusion panel: A single center experience

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Gene fusions, driven by chromosomal rearrangements, are key oncogenic drivers in cancer.
• Traditional detection methods (FISH, RT-PCR, IHC) have limitations in scalability and interpretation.
• Next-generation sequencing (NGS) offers high-throughput detection of genetic abnormalities for cancer patient management.

Purpose of the Study:

• To validate the analytical performance and clinical utility of a custom-designed NGS panel, NYU FUSION-SEQer, for detecting oncogenic gene fusions in solid tumors.
• To assess the panel's accuracy, sensitivity, specificity, and reproducibility.
• To evaluate the panel's capability in identifying known and novel fusion genes for clinical applications.

Main Methods:

• Validation of the Archer Anchored Multiplex PCR (AMP™) technology-based NGS panel, NYU FUSION-SEQer, using RNA sequencing.
• Analysis of 75 retrospective validation samples and 84 prospective clinical samples of solid tumors.
• Assessment of sequencing performance, including target enrichment and lower limit of detection (12.5% tumor fraction at 125 ng RNA input).

Main Results:

• The panel demonstrated robust sequencing performance with strong target enrichment.
• Excellent analytic accuracy was observed: 100% sensitivity, 100% specificity, and 100% reproducibility in validation samples.
• In the prospective cohort, 61% of cases harbored detected fusions, with 41% informing diagnosis and 59% guiding treatment and prognosis.

Conclusions:

• NYU FUSION-SEQer accurately, efficiently, and cost-effectively detects a majority of known fusion genes and novel clinically relevant fusions in solid tumors.
• The panel serves as an excellent tool for the discovery of new fusion genes.
• This NGS-based approach enhances cancer patient management through improved diagnostic and therapeutic insights.