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@ARTICLE{Okonechnikov:186732,
author = {K. Okonechnikov$^*$ and A. Federico$^*$ and D. Schrimpf$^*$
and P. Sievers$^*$ and F. Sahm$^*$ and J. Koster and D.
Jones$^*$ and A. von Deimling$^*$ and S. Pfister$^*$ and M.
Kool$^*$ and A. Korshunov$^*$},
title = {{C}omparison of transcriptome profiles between
medulloblastoma primary and recurrent tumors uncovers novel
variance effects in relapses.},
journal = {Acta Neuropathologica Communications},
volume = {11},
number = {1},
issn = {2051-5960},
address = {London},
publisher = {Biomed Central},
reportid = {DKFZ-2023-00084},
pages = {7},
year = {2023},
note = {#EA:B062#LA:B300#},
abstract = {Nowadays medulloblastoma (MB) tumors can be treated with
risk-stratified approaches with up to $80\%$ success rate.
However, disease relapses occur in approximately $30\%$ of
patients and successful salvage treatment strategies at
relapse remain scarce. Acquired copy number changes or TP53
mutations are known to occur frequently in relapses, while
methylation profiles usually remain highly similar to those
of the matching primary tumors, indicating that in general
molecular subgrouping does not change during the course of
the disease. In the current study, we have used RNA
sequencing data to analyze the transcriptome profiles of 43
primary-relapse MB pairs in order to identify specific
molecular features of relapses within various tumor groups.
Gene variance analysis between primary and relapse samples
demonstrated the impact of age in SHH-MB: the changes in
gene expression relapse profiles were more pronounced in the
younger patients (< 10 years old), which were also
associated with increased DNA aberrations and somatic
mutations at relapse probably driving this effect. For Group
3/4 MB transcriptome data analysis uncovered clear sets of
genes either active or decreased at relapse that are
significantly associated with survival, thus could be
potential predictive markers. In addition, deconvolution
analysis of bulk transcriptome data identified
progression-associated differences in cell type enrichment.
The proportion of undifferentiated progenitors increased in
SHH-MB relapses with a concomitant decrease of
differentiated neuron-like cells, while in Group 3/4 MB
relapses cell cycle activity increases and differentiated
neuron-like cells proportion decreases as well. Thus, our
findings uncovered significant transcriptome changes in the
molecular signatures of relapsed MB and could be potentially
useful for further clinical purposes.},
keywords = {Medulloblastoma (Other) / Prognosis (Other) / Relapses
(Other) / Transcriptomics (Other)},
cin = {B062 / B300 / B360 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)B300-20160331 /
I:(DE-He78)B360-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36635768},
doi = {10.1186/s40478-023-01504-1},
url = {https://inrepo02.dkfz.de/record/186732},
}