Performance and clinical utility of two targeted multigene panels for GIST molecular characterization

TL;DR

This study evaluates two multigene panels for diagnosing gastrointestinal stromal tumors and finds they improve molecular characterization and clinical decision-making.

Contribution

The study introduces and validates two lab-developed NGS panels optimized for GIST molecular profiling.

Findings

72.4% of GIST cases had KIT mutations, and 11.0% had PDGFRA mutations.

The second-level panel identified mutations in 16 of 26 KIT/PDGFRA/BRAF WT cases.

Abstract

Molecular analysis is mandatory in the diagnostic work-up of gastrointestinal stromal tumors (GISTs). Indeed, it is essential for clinical decisions, from patients’ selection for systemic treatment to identifying unrecognized syndromic conditions. Since GISTs are recognized as a heterogeneous family of different clinical entities, molecular analysis should also require a feasible, rapid, and reliable diagnostic workflow. Herein, we present our experience on the performance and clinical utility of two lab-developed multigene-NGS panels specifically built for GIST analysis. Among 163 analyzed GISTs, 72.4% carried KIT mutations while 11.0% were PDGFRA-mutant. Among putative KIT/PDGFRA WT cases that arrived at our attention from an external analysis, nine of 10 were found carrying either KIT or PDGFRA pathogenic mutations by our panel. On 26 KIT/PDGFRA/BRAF WT patients at the first level, the second level panel identified NF1 or SDHA mutations in 16 cases, while 10 patients did not display any mutation, except for two of them found as carriers of SDHC epimutation. This optimized NGS diagnostic approach helps to characterize the molecular profiles of GIST and drastically reduces the number of truly non-KIT and non-PDGFRA-addicted GIST cases.

The online version contains supplementary material available at 10.1038/s41598-025-30548-7.

Figures