Coexistence of IDH1 Mutation and KIAA1549::BRAF Fusion in a Diffuse Glioma: A Case Report With Clinical,...

Isocitrate dehydrogenase (IDH) mutations and KIAA1549::BRAF fusions are traditionally regarded as independent and mutually exclusive genetic events in gliomas. IDH mutations are hallmark features of diffuse gliomas in adults, while KIAA1549::BRAF fusions are characteristic of pediatric pilocytic astrocytomas and diffuse leptomeningeal glioneuronal tumors (DLGNTs). This report presents a rare case of a 31-year-old male with diffuse astrocytoma, CNS WHO Grade 4, exhibiting co-occurrence of an IDH1 mutation (p.R132L) and KIAA1549::BRAF fusion, identified via next-generation sequencing. Histopathology revealed a diffusely infiltrating glial tumor with high mitotic activity, endothelial proliferation, and necrosis. Immunohistochemistry supported the diagnosis, showing ATRX loss, diffuse p53 positivity, and a high Ki67 index. Molecular profiling confirmed the IDH1 mutation, TP53 mutation, CDKN2A loss, and the rare KIAA1549::BRAF fusion. Fluorescence in situ hybridization also confirmed the KIAA1549::BRAF fusion. The coexistence of these alterations challenges the conventional view of mutual exclusivity, highlighting the need for comprehensive molecular profiling in gliomas. IDH mutations lead to oncometabolite accumulation, while KIAA1549::BRAF fusion activates the MAPK pathway. This dual alteration necessitates multimodal therapeutic approaches targeting both pathways. This case emphasizes the importance of integrated diagnostics in glioma classification and personalized treatment, with further research needed to explore the implications of such rare co-occurrences.