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Published on: January 21, 2019
Analytical and clinical validation of CancerMaster, an automated targeted NGS panel, for tumor-only precision
Jingmin Che1, Woo Sun Kwon1, Jaeyoung Kim2
1Song-dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
Abstract:
We developed a CancerMaster-targeted next generation sequencing (NGS) panel covering 524 key genes specifically designed for the multidimensional molecular profiling of solid tumors. We aimed to establish CancerMaster as an asynchronous and parallel one-stop automated analysis pipeline with a reporting system to overcome the delay in existing NGS approaches. This panel can detect common genomic alteration types, including single nucleotide variants/indels and copy number variants (CNVs), fusions, Epstein-Barr virus/human papillomavirus infection, microsatellite instability (MSI), tumor mutational burden (TMB) status, and human leukocyte antigen typing. Using reference materials, CancerMaster demonstrated 100% reproducibility, 99% analytical sensitivity, and high accuracy (94%). Analytical performance for other biomarker classes-including CNVs, fusions, MSI, TMB, and viral detection-was evaluated separately. In a cohort of 668 patients, we identified actionable mutations, including in TP53, KRAS, and PIK3CA, and CNVs, e.g., ERBB2 amplification in gastric (n = 412) and colorectal (n = 66) cancers. MSI and TMB were strongly correlated in all patients (n = 668, r = 0.75; p < 10- 15), with consistent results in the gastric (n = 412, r = 0.75; p < 10- 15) and colorectal (n = 66, r = 0.87; p < 10- 15) cancer groups. Furthermore, directly comparing with the TruSight Oncology 500 (TSO500) panel, CancerMaster demonstrated high concordance while uniquely identifying certain clinically relevant alterations, including an ERBB2 missense mutation. Hence, the CancerMaster panel demonstrated high analytical performance and strong clinical potential for supporting clinical decisions regarding personalized cancer treatment.
Insights
The CancerMaster next-generation sequencing panel offers comprehensive molecular profiling for solid tumors, detecting various genomic alterations and infections efficiently. It shows high accuracy and concordance, supporting personalized cancer treatment decisions.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Next-generation sequencing (NGS) enables comprehensive molecular profiling of solid tumors.
- Existing NGS approaches can face delays in analysis and reporting.
- Multidimensional molecular profiling is crucial for personalized cancer treatment.
Purpose of the Study:
- To develop and validate the CancerMaster NGS panel for solid tumor profiling.
- To establish an automated analysis pipeline to reduce turnaround time.
- To assess the clinical utility of the CancerMaster panel in a patient cohort.
Main Methods:
- Development of a 524-gene targeted NGS panel (CancerMaster).
- Establishment of an asynchronous, parallel, automated analysis pipeline with reporting.
- Validation using reference materials and analysis of a 668-patient cohort.
- Comparison with the TruSight Oncology 500 (TSO500) panel.
Main Results:
- CancerMaster demonstrated 100% reproducibility, 99% analytical sensitivity, and 94% accuracy.
- The panel detected single nucleotide variants/indels, CNVs, fusions, viral infections, MSI, TMB, and HLA typing.
- Actionable mutations and CNVs were identified in gastric and colorectal cancers.
- High correlation between MSI and TMB was observed (r=0.75, p<10^-15).
- CancerMaster showed high concordance with TSO500, uniquely identifying ERBB2 alterations.
Conclusions:
- The CancerMaster panel provides robust analytical performance for multidimensional molecular profiling of solid tumors.
- The automated pipeline overcomes delays in existing NGS approaches.
- CancerMaster has strong clinical potential for guiding personalized cancer therapy.
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