Bujung Hong1, Rouzbeh Banan2, Arne Christians2, Makoto Nakamura3,4, Michael Lalk3, Ulrich Lehmann2, Christian Hartmann2, Joachim K Krauss3. 1. Department of Neurosurgery, Hannover Medical School, MHH, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. hong.bujung@mh-hannover.de. 2. Institute for Pathology, Department for Neuropathology, Hannover Medical School, Hannover, Germany. 3. Department of Neurosurgery, Hannover Medical School, MHH, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. 4. Department of Neurosurgery, Cologne Mehrheim Medical Center, University of Witten/Herdecke, Cologne, Germany.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: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 BRAFV600E 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. RESULTS: 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 H3F3AK27M mutation. One of these also harbored a BRAFV600E 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 BRAFV600E nor a H3F3A mutation but a homozygous CDKN2A/B deletion. CONCLUSIONS: 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 H3F3AK27M mutations indicate that a substantial number of GBMc are "metastatic" or "diaschismatic" lesions. Mutation of BRAFV600E may have a stronger biological significance than H3F3AK27M alterations. In a subset of patients, GBM may arise primarily as a distinct entity in the cerebellum.
Authors: Michael Zhang; Richard Li; Erqi L Pollom; Arya Amini; Savita Dandapani; Gordon Li Journal: J Clin Neurosci Date: 2020-11-06 Impact factor: 1.961
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Authors: Peter Raab; Rouzbeh Banan; Arash Akbarian; Majid Esmaeilzadeh; Madjid Samii; Amir Samii; Helmut Bertalanffy; Ulrich Lehmann; Joachim K Krauss; Heinrich Lanfermann; Christian Hartmann; Roland Brüning Journal: Cancers (Basel) Date: 2022-03-09 Impact factor: 6.639