TY  - JOUR
AU  - Korshunov, Andrey
AU  - Okonechnikov, Konstantin
AU  - Stichel, Damian
AU  - Schrimpf, Daniel
AU  - Delaidelli, Alberto
AU  - Tonn, Svenja
AU  - Mynarek, Martin
AU  - Sievers, Philipp
AU  - Sahm, Felix
AU  - Jones, David
AU  - von Deimling, Andreas
AU  - Pfister, Stefan
AU  - Kool, Marcel
TI  - Gene expression profiling of Group 3 medulloblastomas defines a clinically tractable stratification based on KIRREL2 expression.
JO  - Acta neuropathologica
VL  - 144
SN  - 0001-6322
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2022-01396
SP  - 339–352
PY  - 2022
N1  - #EA:B300#LA:B062# / 144, pages 339–352 (2022)
AB  - Medulloblastomas (MB) molecularly designated as Group 3 (Grp 3) MB represent a more clinically aggressive tumor variant which, as a group, displays heterogeneous molecular characteristics and disease outcomes. Reliable risk stratification of Grp 3 MB would allow for appropriate assignment of patients to aggressive treatment protocols and, vice versa, for sparing adverse effects of high-dose radio-chemotherapy in patients with standard or low-risk tumors. Here we performed RNA-based analysis on an international cohort of 179 molecularly designated Grp 3 MB treated with HIT protocols. We analyzed the clinical significance of differentially expressed genes, thereby developing optimal prognostic subdivision of this MB molecular group. We compared the transcriptome profiles of two Grp 3 MB subsets with various outcomes (76 died within the first 60 months vs. 103 survived this period) and identified 224 differentially expressed genes (DEG) between these two clinical groups (Limma R algorithm, adjusted p-value < 0.05). We selected the top six DEG overexpressed in the unfavorable cohort for further survival analysis and found that expression of all six genes strongly correlated with poor outcomes. However, only high expression of KIRREL2 was identified as an independent molecular prognostic indicator of poor patients' survival. Based on clinical and molecular patterns, four risk categories were outlined for Grp 3 MB patients: i. low-risk: M0-1/MYC non-amplified/KIRREL2 low (n = 48; 5-year OS-95
KW  - Expression (Other)
KW  - Group 3 (Other)
KW  - KIRREL2 (Other)
KW  - Medulloblastoma (Other)
KW  - Prognosis (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:35771282
DO  - DOI:10.1007/s00401-022-02460-1
UR  - https://inrepo02.dkfz.de/record/180534
ER  -