Department of Neurosurgery, Hannover Medical School, MHH, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
Institute for Pathology, Department for Neuropathology, Hannover Medical School, Hannover, Germany.
Acta Neurochir (Wien). 2018 Nov;160(11):2237-2248. doi: 10.1007/s00701-018-3673-y. Epub 2018 Sep 10.
Glioblastomas (GBM) are localized in only less than 1% of patients in the cerebellum. Therefore, tumor characteristics, survival, and the efficacy of therapies are not yet well defined. The present study aims to characterize the molecular features of cerebellar GBM (GBMc) in 8 patients treated with contemporary modality in our institution.
Patients' treatment history, progression-free survival (PFS), and overall survival (OS) were analyzed. All histopathological specimens were re-investigated. EGFR amplification was determined by FISH, H3F3A, and HIST1H3B mutation status and MGMT promoter methylation after bisulfite treatment by pyrosequencing and BRAF V600E by pyrosequencing and immunohistochemistry. TERT promoter mutations were analyzed by Sanger sequencing, CDKN2A/B deletions by digital PCR. The expression of IDH1 R132H, ATRX, and p53 was determined through immunohistochemistry.
Six adults and two children (mean age 36 years) underwent tumor resection via medial or lateral suboccipital craniotomy. The median overall survival (mOS) of the adult patients was 7 months. GBMc from two children demonstrated a H3F3A K27M mutation. One of these also harbored a BRAF V600E mutation and has already had a PFS of 74 months. Mutated IDH1 R132H protein was expressed in 2 GBM from adult patients with previous supratentorial anaplastic astrocytoma. One patient carried a TERT promoter mutation. Another patient initially presented with a thalamic pilocytic astrocytoma. The cerebellar tumor revealed neither a BRAF V600E nor a H3F3A mutation but a homozygous CDKN2A/B deletion.
GBM located in the cerebellum can be found in all age groups. We provide novel molecular genetic data on these rare tumors. Mutated IDH1 R132H protein and H3F3A K27M mutations indicate that a substantial number of GBMc are "metastatic" or "diaschismatic" lesions. Mutation of BRAF V600E may have a stronger biological significance than H3F3A K27M alterations. In a subset of patients, GBM may arise primarily as a distinct entity in the cerebellum.
脑桥小脑角（CPA）的脑胶质瘤（GBM）仅占所有 GBM 患者的不到 1%。因此，肿瘤特征、生存和治疗效果尚不清楚。本研究旨在分析我院 8 例采用现代治疗方法的小脑 GBM（GBMc）患者的分子特征。
分析患者的治疗史、无进展生存期（PFS）和总生存期（OS）。重新检查所有组织病理学标本。通过荧光原位杂交（FISH）、焦磷酸测序确定 EGFR 扩增、H3F3A 和 HIST1H3B 突变状态、MGMT 启动子甲基化，通过焦磷酸测序和免疫组化确定 BRAF V600E。通过 Sanger 测序分析 TERT 启动子突变，通过数字 PCR 分析 CDKN2A/B 缺失。通过免疫组化检测 IDH1 R132H、ATR 和 p53 的表达。
6 名成人和 2 名儿童（平均年龄 36 岁）接受了经内侧或外侧枕下颅开颅切除术。2 名儿童的小脑 GBMc 表现出 H3F3A K27M 突变。其中一名患者还存在 BRAF V600E 突变，PFS 已达 74 个月。2 例成人 GBM 患者的 IDH1 R132H 蛋白表达突变，且之前患有幕上间变性星形细胞瘤。1 例患者携带 TERT 启动子突变。另一位患者最初表现为丘脑毛细胞星形细胞瘤。小脑肿瘤既没有 BRAF V600E 也没有 H3F3A 突变，但存在纯合性 CDKN2A/B 缺失。
小脑 GBM 可发生于所有年龄段。我们提供了这些罕见肿瘤的新的分子遗传学数据。突变的 IDH1 R132H 蛋白和 H3F3A K27M 突变表明，大量的 GBMc 是“转移性”或“分裂性”病变。BRAF V600E 突变可能比 H3F3A K27M 改变具有更强的生物学意义。在一部分患者中，小脑 GBM 可能最初是一种独特的实体。
