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Cerebellar glioblastoma: a clinical series with contemporary molecular analysis

  • Original Article - Brain Tumors
  • Published:
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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.

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Author notes

  1. Christian Hartmann and Joachim K. Krauss contributed equally

  2. Bujung Hong and Rouzbeh Banan contributed equally

Authors and Affiliations

  1. Department of Neurosurgery, Hannover Medical School, MHH, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany

    Bujung Hong, Makoto Nakamura, Michael Lalk & Joachim K. Krauss

  2. Institute for Pathology, Department for Neuropathology, Hannover Medical School, Hannover, Germany

    Rouzbeh Banan, Arne Christians, Ulrich Lehmann & Christian Hartmann

  3. Department of Neurosurgery, Cologne Mehrheim Medical Center, University of Witten/Herdecke, Cologne, Germany

    Makoto Nakamura

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  1. Bujung Hong
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With somatic and germ line profiling, “glioblastoma” or “GBM” appears as an outdated basket even to us neurosurgeons—not as obsolete as “brain cancer” though—consisting of various rogue clone cell assemblies, dependent on age, time, and therapies.

A related issue to “GBM” somatic profilomes is the distribution of primary “GBMs” in the human brain—relating to characteristics of brain tissue at various ages and locations, “favorable” or not so “favorable” for “GBM” oncogenesis.

The human cerebella consists of about 10% of the total weight of the human brain—why is it then that primary cerebellar “GBMs” are exceedingly rare, not by far reaching 10% of all GBMs? Because of the neurons to glial cells ratio in the cerebellum?

With quick browsal, my two neuropathologist neuro-oncology collaborators identified only nine (9) histologically verified obviously primary cerebellar ‘GBMs’ in a population-based neuro-surgical service of 2.7 million citizens during 10 years.

The authors are to be congratulated for drawing attention to the cerebellar “GBMs.” A collaborative search in cancer registries and glioma registries of EU countries for a large cohort of primary cerebellar “GBMs” would unlock mysteries of this rare elusive tumor in an elusive location.

Juha E Jääskeläinen

Kuopio, Finland

This article is part of the Topical Collection on Brain Tumors

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Hong, B., Banan, R., Christians, A. et al. Cerebellar glioblastoma: a clinical series with contemporary molecular analysis. Acta Neurochir 160, 2237–2248 (2018). https://doi.org/10.1007/s00701-018-3673-y

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