Development and Performance Validation of a Comprehensive Liquid Biopsy Genotyping Panel for Pan-cancer Analysis.

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Precision oncology demands advanced non-invasive genomic profiling.
• Liquid biopsy using circulating tumor DNA (ctDNA) offers real-time molecular insights.
• The PAN100 panel is a pan-cancer assay targeting 101 genes for variant detection.

Purpose of the Study:

• To validate the analytical and clinical performance of the PAN100 panel.
• To assess the PAN100 panel's utility in detecting clinically actionable variants across diverse cancer types.
• To establish the accuracy and reliability of the PAN100 panel for liquid biopsy applications.

Main Methods:

• Analytical validation included accuracy, limit of detection (LoD), and precision using reference materials.
• Clinical validation utilized plasma samples from 27 cancer patients and 17 matched tumor tissues.
• Positive percent agreement (PPA) with tissue next-generation sequencing (NGS) was evaluated.

Main Results:

• The PAN100 panel achieved high precision and linearity with an LoD of 0.3% variant allele frequency.
• Overall PPA between ctDNA and tissue NGS was 74.2% (SNVs 73.1%, indels 80.0%).
• The limit of blank (LoB) was determined to be 0.00001%.

Conclusions:

• The PAN100 panel is a robust tool for detecting clinically significant variants with high concordance to tissue NGS.
• Its sensitivity for low-frequency variants supports real-time treatment adaptation in precision oncology.
• The panel's comprehensive design aids in challenging diagnoses and monitoring clonal evolution.