Validation of a targeted sequencing panel with automatic analysis system for clinical decision support in cancer therapy

This is the authors' abstract. We don't add key points for this paper.

Purpose Precision cancer therapy relies on the identification of tumor-specific genomic alterations, which can be achieved through next-generation sequencing (NGS). In the clinic, personalized treatment for patients with advanced treatment-refractory solid tumors often requires rapid and comprehensive multi-dimensional molecular signature analysis using tumor-only samples because paired normal specimens are unavailable in most cases. To address this issue, we developed a CancerMaster panel, targeted NGS panel with 524 key genes specifically designed for multi-dimensional molecular signature analysis of solid tumors. Methods Its asynchronous and parallel one-stop automated analysis pipeline with a reporting system provides a comprehensive solution to shorten the turnaround time from analysis to reporting. The panel can detect common genomic alteration types, including SNVs/Indels and CNVs, fusions, Epstein-Barr virus (EBV)/Human papillomavirus (HPV) infection, microsatellite instability (MSI), tumor mutational burden (TMB) status and human leukocyte antigen (HLA) typing. Results We confirmed its reproducibility (100%) and analytical sensitivity (99%) using reference materials and performed clinical validation of the panel, which demonstrated a high accuracy (94%). Using the CancerMaster panel, we identified actionable mutations (TP53, KRAS, and PIK3CA) and CNV (ERBB2 amplification) mainly in gastric and colorectal cancer. We also found a high correlation between MSI and TMB in our patient samples (n = 668, r = 0.75, p < ), especially for gastric cancer (n = 412, r = 0.75, p < ) and colorectal cancer (n = 66, r = 0.87, p < ). Conclusion The CancerMaster panel demonstrated the potential for clinical decision support in personalized cancer treatment.