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@ARTICLE{Godbole:291810,
author = {S. Godbole and H. Voß and A. Gocke and S. Schlumbohm and
Y. Schumann and B. Peng and M. Mynarek and S. Rutkowski and
M. Dottermusch and M. M. Dorostkar and A. Korshunov$^*$ and
T. Mair and S. Pfister$^*$ and M. Kwiatkowski and M. Hotze
and P. Neumann and C. Hartmann and J. Weis and F.
Liesche-Starnecker and Y. Guan and M. Moritz and B. Siebels
and N. Struve and H. Schlüter and U. Schüller and C. Krisp
and J. E. Neumann},
title = {{M}ultiomic profiling of medulloblastoma reveals
subtype-specific targetable alterations at the proteome and
{N}-glycan level.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2024-01522},
pages = {6237},
year = {2024},
abstract = {Medulloblastomas (MBs) are malignant pediatric brain tumors
that are molecularly and clinically heterogenous. The
application of omics technologies-mainly studying nucleic
acids-has significantly improved MB classification and
stratification, but treatment options are still
unsatisfactory. The proteome and their N-glycans hold the
potential to discover clinically relevant phenotypes and
targetable pathways. We compile a harmonized proteome
dataset of 167 MBs and integrate findings with DNA
methylome, transcriptome and N-glycome data. We show six
proteome MB subtypes, that can be assigned to two main
molecular programs: transcription/translation (pSHHt, pWNT
and pG3myc), and synapses/immunological processes (pSHHs,
pG3 and pG4). Multiomic analysis reveals different
conservation levels of proteome features across MB subtypes
at the DNA methylome level. Aggressive pGroup3myc MBs and
favorable pWNT MBs are most similar in cluster hierarchies
concerning overall proteome patterns but show different
protein abundances of the vincristine resistance-associated
multiprotein complex TriC/CCT and of N-glycan
turnover-associated factors. The N-glycome reflects proteome
subtypes and complex-bisecting N-glycans characterize
pGroup3myc tumors. Our results shed light on targetable
alterations in MB and set a foundation for potential
immunotherapies targeting glycan structures.},
keywords = {Medulloblastoma: metabolism / Medulloblastoma: genetics /
Humans / Polysaccharides: metabolism / Proteome: metabolism
/ Cerebellar Neoplasms: metabolism / Cerebellar Neoplasms:
genetics / DNA Methylation / Transcriptome / Child /
Proteomics: methods / Female / Gene Expression Regulation,
Neoplastic / Male / Child, Preschool / Gene Expression
Profiling: methods / Polysaccharides (NLM Chemicals) /
Proteome (NLM Chemicals)},
cin = {B300 / HD01 / B062},
ddc = {500},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B062-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39043693},
doi = {10.1038/s41467-024-50554-z},
url = {https://inrepo02.dkfz.de/record/291810},
}