Giant cell glioblastoma (G-GBM) is a rare variant of glioblastoma characterized by very large often multinucleated tumour cells. G-GBM occur most frequently de novo; in contrast to IDH wildtype GBM they carry TP53 mutations in high frequency. We performed a systematic (immuno)histological and genetic analysis by MIP, panel NGS and pyrosequencing in a cohort of 58 G-GBM (25 children, 33 adults). 78.4% of G-GBM carried mutations of TP53. Five G-GBM represented IDH-mutated gliomas, 5 cases had H3F3A-G34, and 3 had H3-K27 M mutations. The vast majority (75%) lacked IDH or histone gene mutations. In these, chromosome 7 showed a copy number gain in 2/3 of the cases. TERT promotor mutations occurred only in adult patients at a frequency of 35.5%. Chrom. 1q gain, 10 and 13 loss was more frequent in adults. MGMT promotor was methylated in 30.6% of G-GBM. As a potential therapeutic target, PDGFR-alpha was found expressed in most cases and its gene showed copy number gain in 34.5%. In summary, G-GBM is a histological phenotype most likely related to p53 dysfunction but can occur in different genetically defined GBM entities (IDH-, histone gene mutated or in IDH/histone wildtype GBM).
