Comparison of Large, Medium, and Small Solid Tumor Gene Panels for Detection of Clinically Actionable Mutations in Cancer

Affiliations

PMID: 32770442
DOI: 10.1007/s11523-020-00743-9

Abstract

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.