PDGFRA mutation

Using a 73-gene panel, we characterized the molecular characteristics of GISTs and revealed a correlation with their clinical features. Moreover, KIT/PDGFRA-dependent and KIT/PDGFRA-independent mechanisms underlying resistance to imatinib were explored. Overall, our 73-gene panel is sufficient for clinical application in cases of GISTs.

In addition, NGS identified MDM2 and MYC amplification. This is the first report describing an NF1-mutant GIST harboring coamplification of MDM2 and MYC and associated with a higher-grade tumor progression.

Our findings provided preliminary evidence that novel FGFR2 fusions might act as primary oncogenic drivers in a rare subset of KIT/PDGFRA wild-type GISTs. These cases highlight the importance for comprehensive genomic profiling and suggest that fibroblast growth factor receptor-targeted inhibitors could be a potential therapeutic strategy for advanced or imatinib-resistant diseases, warranting further investigation in larger cohorts.

As one of the 14 defined neuronal and glioneuronal tumors, it is molecularly characterized by PDGFRA p.K385 mutation. In this paper, we illustrate computed tomography, conventional and functional magnetic resonance imaging, and positron emission tomography-computed tomography imaging features of two myxoid glioneuronal tumor cases, introducing novel imaging characteristics.

SDH deficient GIST is a unique subtype of gastrointestinal stromal tumor with distinct clinic-pathological features, diagnostic modalities, therapeutic strategies, and genetic implications as compared to C-kit/PDGFR-alpha mutated GIST.

Second- and third-line TKIs, such as sunitinib and regorafenib, provide limited benefits, highlighting the urgent need to address resistance mechanisms. These findings uncover a TGF-β1/CCN2/Rack1/PGK1 mechanism linking CAF-mediated metabolic reprogramming to imatinib resistance in GISTs. Targeting CAF-GIST interactions and key metabolic pathways presents a promising therapeutic strategy.

CGP revealed actionable alterations in most patients with advanced GISTs; however, its impact on treatment decisions remains limited under current practice. Early CGP implementation may facilitate access to matched therapies or clinical trials, enabling prognostic stratification in patients with advanced GISTs.

P1, N=278, Recruiting, IDRx Inc. - A GSK Company | Trial primary completion date: Mar 2027 --> Nov 2027

P1/2, N=37, Active, not recruiting, Blueprint Medicines Corporation | Trial primary completion date: Feb 2025 --> Nov 2025

Introduction: Gastrointestinal stromal tumors (GISTs) are primarily driven by mutations in KIT (KIT proto-oncogene receptor tyrosine kinase) or PDGFRA (platelet-derived growth factor receptor alpha), but resistance to tyrosine kinase inhibitors (TKIs) such as imatinib remains a major clinical challenge. Although direct evidence remains limited, particularly regarding DNA repair and polymorphisms, FGFR2-targeted therapies (e.g., erdafitinib, pemigatinib) show potential, especially in combination with TKIs or DNA-damaging agents. Future research should prioritize GIST-specific clinical trials, the development of FGFR2-driven models, and standardized molecular diagnostics to validate FGFR2 as a therapeutic target.

However, close postoperative observation is needed because an MGNT often disseminates intracranially and/or into the spinal cord. In addition, we believe that MGNTs located in the septum pellucidum are good candidates for endoscopic resection.