Ion Mobility Mass Spectrometry Enables the Generation of a Ganglioside Atlas in Oligodendroglioma and Matched Peritumoral Tissues

Abstract Oligodendroglioma is a diffuse glioma defined by IDH mutation and whole-arm 1p/19q codeletion. Although gangliosides play essential roles in membrane organization and tumor biology, their molecular diversity in oligodendrogliomas remains poorly understood because of the limited structural resolution of conventional analytical approaches. Gangliosides extracted from paired tumoral and peritumoral tissues from three patients with oligodendroglioma were analyzed using an integrated workflow combining high-performance thin-layer chromatography (HPTLC) and high-resolution cyclic ion mobility mass spectrometry. Molecular annotation included canonical, O-acetylated, and fucosylated ganglioside species. A total of 205 distinct ganglioside molecular species were identified, providing a detailed molecular-species-level characterization of the gangliosidome in the analyzed oligodendroglioma and matched peritumoral tissue. Tumoral tissues contained 184 species, peritumoral tissues contained 171 species, and 148 species were shared, including a set of 55 ganglioside molecular species detected in all samples. Oligodendroglioma retained a diverse inventory of complex GD-, GT-, GQ-, and GP-series gangliosides together with numerous O-acetylated and fucosylated structures. Despite greater molecular diversity in tumors, the overall ganglioside class distribution and ceramide composition remained largely conserved, indicating that the remodeling process predominantly affects glycan head groups rather than the ceramide scaffold. This study provides the first detailed cyclic ion mobility mass spectrometry (cIMS-MS) characterization of the gangliosidome in isocitrate dehydrogenase (IDH) mutant, 1p/19q-codeleted oligodendroglioma. The findings substantially expand the known molecular diversity of this tumor type and identify selective glycan alterations with the preservation of ceramide architecture as a defining molecular feature, providing a framework for future biomarker discovery and mechanistic studies of glycosphingolipid metabolism in diffuse gliomas.