Characteristics of cerebellar glioblastomas in adults

Abstract

Adult cerebellar glioblastomas (cGBM) are rare and their characteristics remain to be fully described. We analyzed the characteristics of 17 adult patients with cGBM and compared them to a series of 103 patients presenting a supra-tentorial glioblastoma (stGBM). The mean age at GBMc diagnosis was 53.4 years (range 28-77). A history of neurofibromatosis type I was noted in 3 patients. cGBM were hemispheric in 10 patients (58.8%), only vermian in 4 patients (23.5%), and both vermian and hemispheric in 3 patients (17.7%). A H3 K27M mutation was identified in 3/14 patients, a TERT promoter mutation in 3/14 patients and a methylated MGMT promoter in 3/14 patients. None of the patients (0/14) harbored an EGFR amplification, an IDH or a BRAF mutation. Association with neurofibromatosis type I and H3K27M mutations were mutually exclusive. Compared with stGBM, cGBM occurred in younger patients (53.4 vs. 63.2, p = 0.02), were more frequently associated with neurofibromatosis type I (18 vs. 1%, p = 0.009) and with a H3 K27M mutation (21 vs. 3%, p = 0.02). They also tended to have a more frequent multifocal presentation at diagnosis (21 vs. 4.3%, p = 0.06), more frequently resulted in leptomeningeal or intra-axial metastasis (44.5 vs. 5%, p = 0.002) and were associated with a shorter median overall survival (5.9 vs. 14.2 months, p = 0.004). The present study suggests that adult cGBM differ from their supra-tentorial counterpart and constitute a heterogeneous group of IDH wild-type gliomas with at least two subgroups, one associated with H3K27M mutations and the other with neurofibromatosis type I.

TERT promoter wild-type glioblastomas show distinct clinical features and frequent PI3K pathway mutations

“…In addition, we identified a significantly higher rate of cerebellar GBM in the TERT p-wt compared with the TERT p mutant patients. Our finding is consistent with prior studies that have shown that cerebellar GBMs occur in patients that are younger than patients with supratentorial GBMs, and have decreased frequency in TERT p mutations and more frequent NF1 mutations [ 16 , 20 ]. Taken together with our findings, these data support the proposal that cerebellar GBMs may comprise a distinct subclass of tumor, which may arise via an alternative molecular etiology when compared to supratentorial TERT p mutant GBM.…”

The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis

“…Finally, a total of nine studies were included for meta-analyses comprising of 2819 glioma patients ( Fig. 1) [16,[25][26][27][28][29][30][31][32]. The baseline characteristics of these studies were presented in Table 1.…”

cIMPACT-NOW update 3: recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”

“…Signatures predictive of aggressive clinical behavior will not apply to most pediatric diffuse gliomas and may not be relevant to diffuse gliomas arising in other less common sites. For example, IDH-wildtype diffuse astrocytic gliomas that arise in the cerebellum of adults are rare, and recent studies indicate that they do not harbor the same percentage of EGFR amplification, +7/−10, or TERT promoter mutations as their supratentorial counterparts[22, 23]. A subset will harbor H3 K27 or SETD2 mutations, but the full spectrum of their other alterations have not been defined, nor have the genetic events corresponding to aggressive behavior.…”