Comprehensive NGS Panel Validation for the Identification of Actionable Alterations in Adult Solid Tumors

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Advancements in targeted therapies necessitate comprehensive molecular profiling of tumors.
• Standard molecular methods face challenges in clinical translation compared to next-generation sequencing (NGS) panels.
• Clinical accreditation requires adherence to high-quality standards for NGS assays.

Purpose of the Study:

• To evaluate the analytical and clinical feasibility of a hybridization capture-based NGS panel, Action OncoKitDx.
• To assess the panel's capability in detecting somatic mutations, copy number variants (CNVs), fusions, pharmacogenetic SNPs, and Microsatellite Instability (MSI).
• To determine the clinical utility of the assay in formalin-fixed paraffin-embedded (FFPE) tumor samples across various tumor types.

Main Methods:

• Analytical validation using 64 samples for known variant identification.
• Clinical utility assessment with 166 tumor and matched normal samples.
• Hybridization capture-based NGS panel (Action OncoKitDx) for FFPE tumor analysis.

Main Results:

• The panel demonstrated high specificity, sensitivity, reproducibility, and repeatability for all analyzed biomarkers.
• A 5% limit of detection was successfully validated.
• Pathogenic genomic alterations were identified in 97% of patient cases, with 82.7% showing at least one clinically relevant variant.

Conclusions:

• The Action OncoKitDx assay is accurate and robust for analyzing adult solid tumors.
• The panel's comprehensive biomarker detection supports its utility in clinical practice.
• Validated performance characteristics enable the clinical translation of this NGS assay.