Clinicopathological and molecular features of wild-type gastrointestinal stromal tumors identified by targeted NGS.

BACKGROUND: mutations. These tumors pose significant diagnostic and therapeutic challenges due to resistance to standard tyrosine kinase inhibitors and a wide spectrum of genetic drivers. METHODS: A total of 156 GIST patients were retrospectively reviewed, among whom 19 WT GIST cases were identified. Immunohistochemistry, Sanger sequencing, and targeted next-generation sequencing (NGS) covering 39 cancer-related genes were performed to evaluate clinicopathological and molecular characteristics. Variants were annotated and filtered using public mutation databases. CONCLUSION: WT GISTs exhibit considerable molecular heterogeneity with novel or rare mutations of uncertain significance. Targeted NGS enables the detection of clinically relevant alterations that may guide future diagnostic and therapeutic strategies. Our findings emphasize the importance of targeted molecular profiling and raise the potential for personalized treatment in this challenging subset of GISTs.