TY  - JOUR
AU  - Suwala, Abigail Kora
AU  - Stichel, Damian
AU  - Schrimpf, Daniel
AU  - Maas, Sybren L N
AU  - Sill, Martin
AU  - Dohmen, Hildegard
AU  - Banan, Rouzbeh
AU  - Reinhardt, Annekathrin
AU  - Sievers, Philipp
AU  - Hinz, Felix
AU  - Blattner-Johnson, Mirjam
AU  - Hartmann, Christian
AU  - Schweizer, Leonille
AU  - Boldt, Henning B
AU  - Kristensen, Bjarne Winther
AU  - Schittenhelm, Jens
AU  - Wood, Matthew D
AU  - Chotard, Guillaume
AU  - Bjergvig, Rolf
AU  - Das, Anirban
AU  - Tabori, Uri
AU  - Hasselblatt, Martin
AU  - Korshunov, Andrey
AU  - Abdullaev, Zied
AU  - Quezado, Martha
AU  - Aldape, Kenneth
AU  - Harter, Patrick
AU  - Snuderl, Matija
AU  - Hench, Jürgen
AU  - Frank, Stephan
AU  - Acker, Till
AU  - Brandner, Sebastian
AU  - Winkler, Frank
AU  - Wesseling, Pieter
AU  - Pfister, Stefan M
AU  - Reuss, David E
AU  - Wick, Wolfgang
AU  - von Deimling, Andreas
AU  - Jones, David T W
AU  - Sahm, Felix
TI  - Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1.
JO  - Acta neuropathologica
VL  - 142
IS  - 1
SN  - 1432-0533
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2021-00909
SP  - 179-189
PY  - 2021
N1  - #EA:B300#LA:B300# /2021 Jul;142(1):179-189
AB  - Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.
KW  - Classification (Other)
KW  - DNA methylation (Other)
KW  - GBM (Other)
KW  - PNET (Other)
KW  - Phenotype (Other)
KW  - Plasticity (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33876327
DO  - DOI:10.1007/s00401-021-02302-6
UR  - https://inrepo02.dkfz.de/record/168435
ER  -