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Updated: Dec 12, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Comparison of Large, Medium, and Small Solid Tumor Gene Panels for Detection of Clinically Actionable Mutations in
Eric Vail1,2, Jianbo Song3, Jing Xu3
1Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Eric.Vail@cshs.org.
Background:
Next-generation sequencing of gene panels has supplanted single-gene testing for cancer molecular diagnostics in many laboratories. Considerations for the optimal number of genes to assess in a panel depend on the purpose of the testing.
Objective:
To address the optimal size for the identification of clinically actionable variants in different-sized solid tumor sequencing panels.
Patients And Methods:
Sequencing results from 480 patients with a large, 315 gene, panel were compared against coverage of a medium, 161 gene, and small, 50 gene, panel.
Results:
The large panel detected a total of 2072 sequence variants in 480 patient specimens; 61 (12.7%) contained variants for which there is therapy approved by the US Food and Drug Administration, 89 (18.5%) had variants associated with an off-label therapy, and 312 (65.0%) contained variants eligible for a genomically matched clinical trial. The small panel covered only 737 of the 2072 variants (35.5%) and somewhat fewer therapy-related variants (on-label 88.5%, off-label 60.7%). The medium-size panel included 1354 of the 2072 (65.3%) variants reported by the large panel. All 318 patients with a clinically actionable variant would have been identified by the medium panel.
Conclusions:
The results demonstrate that a carefully designed medium size gene panel is as effective as a large panel for the detection of clinically actionable variants and can be run by most molecular pathology laboratories.
Insights
A medium-sized gene panel effectively identifies actionable cancer variants, comparable to larger panels. This finding supports the use of medium panels in molecular pathology labs for cancer diagnostics.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Next-generation sequencing (NGS) gene panels are increasingly used for cancer molecular diagnostics, replacing single-gene tests.
- The optimal gene panel size is crucial and depends on the specific diagnostic application.
Purpose of the Study:
- To determine the ideal size of gene panels for identifying clinically actionable variants in solid tumors.
- To compare the performance of different-sized gene panels (small, medium, large) in detecting actionable mutations.
Main Methods:
- Sequencing data from 480 patients using a large 315-gene panel were analyzed.
- The coverage and variant detection of the large panel were compared against a 161-gene medium panel and a 50-gene small panel.
Main Results:
- The large panel identified 2072 variants; 12.7% had FDA-approved therapies, 18.5% had off-label therapy associations, and 65.0% were eligible for clinical trials.
- A medium-sized panel detected 65.3% of variants found by the large panel and would have identified all patients with actionable variants.
- A small panel identified only 35.5% of variants and missed a significant number of actionable mutations.
Conclusions:
- A well-designed medium-sized gene panel is as effective as a large panel for detecting clinically actionable variants in solid tumors.
- Medium-sized gene panels are practical for implementation in most molecular pathology laboratories, offering a balance of comprehensive detection and efficiency.
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