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@ARTICLE{Korshunov:275602,
author = {A. Korshunov$^*$ and K. Okonechnikov$^*$ and D.
Schrimpf$^*$ and S. Tonn and M. Mynarek and J. Koster and P.
Sievers$^*$ and T. Milde$^*$ and F. Sahm$^*$ and D.
Jones$^*$ and A. von Deimling$^*$ and S. Pfister$^*$ and M.
Kool$^*$},
title = {{T}ranscriptome analysis stratifies second-generation
non-{WNT}/non-{SHH} medulloblastoma subgroups into
clinically tractable subtypes.},
journal = {Acta neuropathologica},
volume = {145},
number = {6},
issn = {0001-6322},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2023-00812},
pages = {829-842},
year = {2023},
note = {#EA:B300#LA:B062# / 2023 Jun;145(6):829-842},
abstract = {Medulloblastoma (MB), one of the most common malignant
pediatric brain tumor, is a heterogenous disease comprised
of four distinct molecular groups (WNT, SHH, Group 3, Group
4). Each of these groups can be further subdivided into
second-generation MB (SGS MB) molecular subgroups, each with
distinct genetic and clinical characteristics. For instance,
non-WNT/non-SHH MB (Group 3/4) can be subdivided molecularly
into eight distinct and clinically relevant tumor subgroups.
A further molecular stratification/summarization of these
SGS MB would allow for the assignment of patients to
risk-associated treatment protocols. Here, we performed DNA-
and RNA-based analysis of 574 non-WNT/non-SHH MB and
analyzed the clinical significance of various molecular
patterns within the entire cohort and the eight SGS MB, with
the aim to develop an optimal risk stratification of these
tumors. Multigene analysis disclosed several
survival-associated genes highly specific for each molecular
subgroup within this non-WNT/non-SHH MB cohort with minimal
inter-subgroup overlap. These subgroup-specific and
prognostically relevant genes were associated with pathways
that could underlie SGS MB clinical-molecular diversity and
tumor-driving mechanisms. By combining survival-associated
genes within each SGS MB, distinct metagene sets being
appropriate for their optimal risk stratification were
identified. Defined subgroup-specific metagene sets were
independent variables in the multivariate models generated
for each SGS MB and their prognostic value was confirmed in
a completely non-overlapping validation cohort of
non-WNT/non-SHH MB (n = 377). In summary, the current
results indicate that the integration of transcriptome data
in risk stratification models may improve outcome prediction
for each non-WNT/non-SHH SGS MB. Identified
subgroup-specific gene expression signatures could be
relevant for clinical implementation and survival-associated
metagene sets could be adopted for further SGS MB risk
stratification. Future studies should aim at validating the
prognostic role of these transcriptome-based SGS MB subtypes
in prospective clinical trials.},
keywords = {Medulloblastoma (Other) / Non-WNT/non-SHH (Other) /
Prognosis (Other) / Subgroups (Other) / Transcriptomic
(Other)},
cin = {B300 / HD01 / B062 / B360 / B310},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)B360-20160331 /
I:(DE-He78)B310-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37093271},
doi = {10.1007/s00401-023-02575-z},
url = {https://inrepo02.dkfz.de/record/275602},
}