Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities

TY - JOUR

T1 - Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities

AU - Reinhardt, Annekathrin

AU - Stichel, Damian

AU - Schrimpf, Daniel

AU - Koelsche, Christian

AU - Wefers, Annika K

AU - Ebrahimi, Azadeh

AU - Sievers, Philipp

AU - Huang, Kristin

AU - Casalini, M Belén

AU - Fernández-Klett, Francisco

AU - Suwala, Abigail

AU - Weller, Michael

AU - Gramatzki, Dorothee

AU - Felsberg, Joerg

AU - Reifenberger, Guido

AU - Becker, Albert

AU - Hans, Volkmar H

AU - Prinz, Marco

AU - Staszewski, Ori

AU - Acker, Till

AU - Dohmen, Hildegard

AU - Hartmann, Christian

AU - Paulus, Werner

AU - Heß, Katharina

AU - Brokinkel, Benjamin

AU - Schittenhelm, Jens

AU - Buslei, Rolf

AU - Deckert, Martina

AU - Mawrin, Christian

AU - Hewer, Ekkehard

AU - Pohl, Ute

AU - Jaunmuktane, Zane

AU - Brandner, Sebastian

AU - Unterberg, Andreas

AU - Hänggi, Daniel

AU - Platten, Michael

AU - Pfister, Stefan M

AU - Wick, Wolfgang

AU - Herold-Mende, Christel

AU - Korshunov, Andrey

AU - Reuss, David E

AU - Sahm, Felix

AU - Jones, David T W

AU - Capper, David

AU - von Deimling, Andreas

PY - 2019/10/28

Y1 - 2019/10/28

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Cerebellar Neoplasms/diagnosis

KW - Child

KW - Child, Preschool

KW - Cyclin-Dependent Kinase Inhibitor p16/metabolism

KW - ErbB Receptors/metabolism

KW - Female

KW - Glioblastoma/diagnosis

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Infratentorial Neoplasms/diagnosis

KW - Male

KW - Methylation

KW - Middle Aged

KW - Retrospective Studies

KW - Telomerase/metabolism

KW - Young Adult

U2 - 10.1186/s40478-019-0801-8

DO - 10.1186/s40478-019-0801-8

M3 - SCORING: Journal article

C2 - 31661039

VL - 7

SP - 163

JO - ACTA NEUROPATHOL COM

JF - ACTA NEUROPATHOL COM

SN - 2051-5960

IS - 1

ER -