Reinhardt, Annekathrin, Stichel, Damian, Schrimpf, Daniel, Koelsche, Christian, Wefers, Annika K., Ebrahimi, Azadeh, Sievers, Philipp, Huang, Kristin, Casalini, M. Belen, Fernandez-Klett, Francisco, Suwala, Abigail, Weller, Michael, Gramatzki, Dorothee, Felsberg, Joerg, Reifenberger, Guido, Becker, Albert, Hans, Volkmar H., Prinz, Marco, Staszewski, Ori, Acker, Till, Dohmen, Hildegard, Hartmann, Christian, Paulus, Werner, Hess, Katharina ORCID: 0000-0003-3922-6413, Brokinkel, Benjamin, Schittenhelm, Jens, Buslei, Rolf, Deckert, Martina, Mawrin, Christian, Hewer, Ekkehard ORCID: 0000-0002-9128-0364, Pohl, Ute, Jaunmuktane, Zane ORCID: 0000-0001-7738-8881, Brandner, Sebastian, Unterberg, Andreas, Haenggi, Daniel, Platten, Michael ORCID: 0000-0002-4746-887X, Pfister, Stefan M., Wick, Wolfgang, Herold-Mende, Christel, Korshunov, Andrey ORCID: 0000-0002-5257-3623, Reuss, David E., Sahm, Felix ORCID: 0000-0001-5441-1962, Jones, David T. W., Capper, David and von Deimling, Andreas ORCID: 0000-0002-5863-540X (2019). Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities. Acta Neuropathol. Commun., 7 (1). LONDON: BMC. ISSN 2051-5960

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Reinhardt, AnnekathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stichel, DamianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schrimpf, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koelsche, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wefers, Annika K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebrahimi, AzadehUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sievers, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huang, KristinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Casalini, M. BelenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez-Klett, FranciscoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suwala, AbigailUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weller, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gramatzki, DorotheeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Felsberg, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reifenberger, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, AlbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hans, Volkmar H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prinz, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Staszewski, OriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Acker, TillUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dohmen, HildegardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paulus, WernerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hess, KatharinaUNSPECIFIEDorcid.org/0000-0003-3922-6413UNSPECIFIED
Brokinkel, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schittenhelm, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buslei, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deckert, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mawrin, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hewer, EkkehardUNSPECIFIEDorcid.org/0000-0002-9128-0364UNSPECIFIED
Pohl, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaunmuktane, ZaneUNSPECIFIEDorcid.org/0000-0001-7738-8881UNSPECIFIED
Brandner, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Unterberg, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haenggi, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Platten, MichaelUNSPECIFIEDorcid.org/0000-0002-4746-887XUNSPECIFIED
Pfister, Stefan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wick, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herold-Mende, ChristelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korshunov, AndreyUNSPECIFIEDorcid.org/0000-0002-5257-3623UNSPECIFIED
Reuss, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sahm, FelixUNSPECIFIEDorcid.org/0000-0001-5441-1962UNSPECIFIED
Jones, David T. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Capper, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Deimling, AndreasUNSPECIFIEDorcid.org/0000-0002-5863-540XUNSPECIFIED
URN: urn:nbn:de:hbz:38-130251
DOI: 10.1186/s40478-019-0801-8
Journal or Publication Title: Acta Neuropathol. Commun.
Volume: 7
Number: 1
Date: 2019
Publisher: BMC
Place of Publication: LONDON
ISSN: 2051-5960
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TERT PROMOTER MUTATIONS; H3 K27M MUTATIONS; PROGNOSTIC-FACTORS; CLASSIFICATION; ADULTS; IMPACTMultiple languages
NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13025

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