Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities.

Reinhardt, Annekathrin; Stichel, Damian; Schrimpf, Daniel; Koelsche, Christian; Wefers, Annika K; Ebrahimi, Azadeh; Sievers, Philipp; Huang, Kristin; Casalini, M Belén; Fernández-Klett, Francisco; Suwala, Abigail; Weller, Michael; Gramatzki, Dorothee; Felsberg, Joerg; Reifenberger, Guido; Becker, Albert; Hans, Volkmar H; Prinz, Marco; Staszewski, Ori; Acker, Till; ... (2019). Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities. Acta neuropathologica communications, 7(1), p. 163. BioMed Central 10.1186/s40478-019-0801-8

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Hewer, Ekkehard

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2051-5960

Publisher:

BioMed Central

Language:

English

Submitter:

Ekkehard Hewer

Date Deposited:

11 Nov 2019 10:44

Last Modified:

24 Nov 2019 02:44

Publisher DOI:

10.1186/s40478-019-0801-8

PubMed ID:

31661039

Uncontrolled Keywords:

Anaplastic astrocytoma with piloid features Anaplastic pilocytic astrocytoma Cerebellar glioblastoma Copy number variation load Integrated diagnosis Methylation-based classification

BORIS DOI:

10.7892/boris.134622

URI:

https://boris.unibe.ch/id/eprint/134622

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