Comprehensive Genomic Profiling for Precision Oncology: Analytical Validation and Clinical Utility in Solid Tumors.

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Comprehensive genomic profiling (CGP) is crucial for precision oncology in solid tumors.
• Clinical implementation requires rigorous analytical validation of CGP assays.
• Validated CGP platforms are needed for routine clinical use.

Purpose of the Study:

• To evaluate the analytical and clinical performance of a comprehensive genomic profiling (CGP) assay.
• To assess the assay's capability in detecting diverse genomic alterations (SNVs, Indels, CNVs, fusions, TMB).
• To determine the assay's suitability for routine clinical deployment in precision oncology.

Main Methods:

• Validation using 117 patient-derived FFPE tumor samples, proficiency testing materials, and reference standards.
• Assessment of assay performance against orthogonal methods, including reproducibility, limit of detection, and TMB concordance.
• Evaluation of sensitivity, specificity, and accuracy for variant detection.

Main Results:

• The CGP assay achieved 100% sensitivity, specificity, and accuracy for variant detection.
• High concordance for tumor mutational burden (TMB) estimation (R² = 0.9925) and classification of TMB-high cases.
• Robust reproducibility and reliable detection of low-frequency variants and RNA fusions.

Conclusions:

• The validated CGP assay offers accurate, reproducible, and comprehensive genomic alteration detection in solid tumors.
• The assay is suitable for routine clinical deployment, supporting precision oncology treatment decisions.
• Reliable genomic profiling through this CGP assay aids in guiding targeted therapies.