PDGFRA K385 mutants in myxoid glioneuronal tumors promote receptor dimerization and oncogenic signaling

Myxoid glioneuronal tumors (MGNT) are low-grade glioneuronal neoplasms composed of oligodendrocyte-like cells in a mucin-rich stroma. These tumors feature a unique dinucleotide change at codon 385 in the platelet-derived growth factor receptor α (encoded by the PDGFRA gene), resulting in the substitution of lysine 385 into leucine or isoleucine. The functional consequences of these mutations remain largely unexplored. Our results provide valuable insights into the molecular mechanism underlying the activation of PDGFRα by the K385I/L mutations, highlighting their potential as actionable targets in the treatment of myxoid glioneuronal tumors.