High-grade gliomas derived from an ovarian mature teratoma: clonal dynamics and genetic insights.
UNLABELLED: High-grade glioma (HGG) arising from a mature ovarian teratoma is extremely rare and its genetic alterations remain largely unknown. We report a case of WHO Grade 4 HGG (HGG-G4) developing 3 years after cystectomy for ovarian mature teratoma, where a WHO Grade 3 HGG (HGG-G3) was identified upon pathological reevaluation. Whole-exome sequencing confirmed the clonal relationship between HGG-G3 and HGG-G4, revealing genome-wide copy-neutral loss of heterozygosity, copy-number alterations, and whole-genome doubling in both HGGs. Genomic and epigenetic analyses have suggested multistep tumorigenesis and clonal alteration during the clinical course, particularly in response to chemotherapy, in HGGs arising from ovarian teratomas. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-025-00790-x.