Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_C246069A68BB
Type
Article: article from journal or magazin.
Collection
Publications
Title
Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities.
Journal
Acta neuropathologica communications
Author(s)
Reinhardt A., Stichel D., Schrimpf D., Koelsche C., Wefers A.K., Ebrahimi A., Sievers P., Huang K., Casalini M.B., Fernández-Klett F., Suwala A., Weller M., Gramatzki D., Felsberg J., Reifenberger G., Becker A., Hans V.H., Prinz M., Staszewski O., Acker T., Dohmen H., Hartmann C., Paulus W., Heß K., Brokinkel B., Schittenhelm J., Buslei R., Deckert M., Mawrin C., Hewer E., Pohl U., Jaunmuktane Z., Brandner S., Unterberg A., Hänggi D., Platten M., Pfister S.M., Wick W., Herold-Mende C., Korshunov A., Reuss D.E., Sahm F., Jones DTW, Capper D., von Deimling A.
ISSN
2051-5960 (Electronic)
ISSN-L
2051-5960
Publication state
Published
Issued date
28/10/2019
Peer-reviewed
Oui
Volume
7
Number
1
Pages
163
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
In this multi-institutional study we compiled a retrospective cohort of 86 posterior fossa tumors having received the diagnosis of cerebellar glioblastoma (cGBM). All tumors were reviewed histologically and subjected to array-based methylation analysis followed by algorithm-based classification into distinct methylation classes (MCs). The single MC containing the largest proportion of 25 tumors diagnosed as cGBM was MC anaplastic astrocytoma with piloid features representing a recently-described molecular tumor entity not yet included in the WHO Classification of Tumours of the Central Nervous System (WHO classification). Twenty-nine tumors molecularly corresponded to either of 6 methylation subclasses subsumed in the MC family GBM IDH wildtype. Further we identified 6 tumors belonging to the MC diffuse midline glioma H3 K27 M mutant and 6 tumors allotted to the MC IDH mutant glioma subclass astrocytoma. Two tumors were classified as MC pilocytic astrocytoma of the posterior fossa, one as MC CNS high grade neuroepithelial tumor with BCOR alteration and one as MC control tissue, inflammatory tumor microenvironment. The methylation profiles of 16 tumors could not clearly be assigned to one distinct MC. In comparison to supratentorial localization, the MC GBM IDH wildtype subclass midline was overrepresented, whereas the MCs GBM IDH wildtype subclass mesenchymal and subclass RTK II were underrepresented in the cerebellum. Based on the integration of molecular and histological findings all tumors received an integrated diagnosis in line with the WHO classification 2016. In conclusion, cGBM does not represent a molecularly uniform tumor entity, but rather comprises different brain tumor entities with diverse prognosis and therapeutic options. Distinction of these molecular tumor classes requires molecular analysis. More than 30% of tumors diagnosed as cGBM belong to the recently described molecular entity of anaplastic astrocytoma with piloid features.
Keywords
Adolescent, Adult, Aged, Aged, 80 and over, Cerebellar Neoplasms/diagnosis, Cerebellar Neoplasms/metabolism, Cerebellar Neoplasms/pathology, Child, Child, Preschool, Cyclin-Dependent Kinase Inhibitor p16/metabolism, ErbB Receptors/metabolism, Female, Glioblastoma/diagnosis, Glioblastoma/metabolism, Glioblastoma/pathology, Humans, Infant, Infant, Newborn, Infratentorial Neoplasms/diagnosis, Infratentorial Neoplasms/metabolism, Infratentorial Neoplasms/pathology, Male, Methylation, Middle Aged, Retrospective Studies, Telomerase/metabolism, Young Adult, Anaplastic astrocytoma with piloid features, Anaplastic pilocytic astrocytoma, Cerebellar glioblastoma, Copy number variation load, Integrated diagnosis, Methylation-based classification
Pubmed
Web of science
Open Access
Yes
Create date
31/08/2020 13:02
Last modification date
10/11/2020 7:26
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