TY  - JOUR
AU  - Geisenberger, Christoph
AU  - Mock, Andreas
AU  - Warta, Rolf
AU  - Rapp, Carmen
AU  - Schwager, Christian
AU  - Korshunov, Andrey
AU  - Nied, Ann-Katrin
AU  - Capper, David
AU  - Brors, Benedikt
AU  - Jungk, Christine
AU  - Jones, David
AU  - Collins, V Peter
AU  - Ichimura, Koichi
AU  - Bäcklund, L Magnus
AU  - Schnabel, Elena
AU  - Mittelbron, Michel
AU  - Lahrmann, Bernd
AU  - Zheng, Siyuan
AU  - Verhaak, Roel G W
AU  - Grabe, Niels
AU  - Pfister, Stefan
AU  - Hartmann, Christian
AU  - von Deimling, Andreas
AU  - Debus, Jürgen
AU  - Unterberg, Andreas
AU  - Abdollahi, Amir
AU  - Herold-Mende, Christel
TI  - Molecular profiling of long-term survivors identifies a subgroup of glioblastoma characterized by chromosome 19/20 co-gain.
JO  - Acta neuropathologica
VL  - 130
IS  - 3
SN  - 1432-0533
CY  - Berlin
PB  - Springer
M1  - DKFZ-2017-02605
SP  - 419 - 434
PY  - 2015
AB  - Glioblastoma (GBM) is a devastating tumor and few patients survive beyond 3 years. Defining the molecular determinants underlying long-term survival is essential for insights into tumor biology and biomarker identification. We therefore investigated homogeneously treated, IDH (wt) long-term (LTS, n = 10) and short-term survivors (STS, n = 6) by microarray transcription profiling. While there was no association of clinical parameters and molecular subtypes with long-term survival, STS tumors were characterized by differential polarization of infiltrating microglia with predominance of the M2 phenotype detectable both on the mRNA and protein level. Furthermore, transcriptional signatures of LTS and STS predicted patient outcome in a large, IDH (wt) cohort (n = 468). Interrogation of overlapping genomic alterations identified concurrent gain of chromosomes 19 and 20 as a favorable prognostic marker. The strong association of this co-gain with survival was validated by aCGH in a second, independent cohort (n = 124). Finally, FISH and gene expression data revealed gains to constitute low-amplitude, clonal events with a strong impact on transcription. In conclusion, these findings provide important insights into the manipulation of the innate immune system by particularly aggressive GBM tumors. Furthermore, we genomically characterize a previously unknown, clinically relevant subgroup of glioblastoma, which can easily be identified through modern neuropathological workup.
KW  - RNA, Messenger (NLM Chemicals)
KW  - Isocitrate Dehydrogenase (NLM Chemicals)
KW  - IDH1 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25931051
DO  - DOI:10.1007/s00401-015-1427-y
UR  - https://inrepo02.dkfz.de/record/126577
ER  -