TY  - JOUR
AU  - Reuss, David E
AU  - Schrimpf, Daniel
AU  - Cherkezov, Asan
AU  - Suwala, Abigail K
AU  - Lausová, Tereza
AU  - Snuderl, Matija
AU  - Capper, David
AU  - Sill, Martin
AU  - Jones, David T W
AU  - Pfister, Stefan M
AU  - Sahm, Felix
AU  - von Deimling, Andreas
TI  - Heterogeneity of DNA methylation profiles and copy number alterations in 10782 adult-type glioblastomas, IDH-wildtype.
JO  - Free Neuropathology
VL  - 5
IS  - 7
SN  - 2699-4445
CY  - Muenster
PB  - Prof. Dr. Werner Paulus, University of Muenster, Institute of Neuropathology
M1  - DKFZ-2024-00607
SP  - 5-7
PY  - 2024
N1  - #EA:B300#LA:B300# / 2024 Mar 22:5:5-7
AB  - The morphological patterns leading to the diagnosis of glioblastoma may also commonly be observed in several other distinct tumor entities, which can result in a mixed bag of tumors subsumed under this diagnosis. The 2021 WHO Classification of CNS Tumors has separated several of these entities from the diagnosis of glioblastoma, IDH-wildtype. This study determines the DNA methylation classes most likely receiving the diagnosis glioblastoma, IDH wildtype according to the definition by the WHO 2021 Classification and provides comparative copy number analyses. We identified 10782 methylome datasets uploaded to the web page www.molecularneuropathology.org with a calibrated score of ≥0.9 by the Heidelberg Brain Tumor Classifier version v12.8. These methylation classes were characterized by the diagnosis glioblastoma being the most frequent classification encountered in each of the classes according to the WHO 2021 definition. Further, methylation classes selected for this study predominantly contained adult patients. Unsupervised clustering confirmed the presence of nine methylation classes containing tumors most likely receiving the diagnosis glioblastoma, IDH-wildtype according to the WHO 2021 definition. Copy number analysis and a focus on genes with typical numerical alterations in glioblastoma revealed clear differences between the nine methylation classes. Although great progress in diagnostic precision has been achieved over the last decade, our data clearly demonstrate that glioblastoma, IDH-wildtype still is a heterogeneous group in need of further stratification.
KW  - 7/10 signature (Other)
KW  - Amplification (Other)
KW  - CDKN2A/B (Other)
KW  - CNV (Other)
KW  - Classification (Other)
KW  - Copy Number Variations (Other)
KW  - EGFR (Other)
KW  - Glioblastoma (Other)
KW  - Homozygous deletion (Other)
KW  - Methylation (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38532825
C2  - pmc:PMC10964111
DO  - DOI:10.17879/FREENEUROPATHOLOGY-2024-5345
UR  - https://inrepo02.dkfz.de/record/289140
ER  -