Metabolomics

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Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level (Amino acid profiling)


ABSTRACT:

Medulloblastomas (MBs) are malignant pediatric brain tumors that are molecularly and clinically very 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 reflect the phenotype of a tumor in a more direct way and thus hold the potential to discover clinically relevant phenotypes and targetable pathways. We compiled a harmonized proteome dataset of 167 MBs and integrated findings with DNA methylome and N-glycome data. Six proteome MB subtypes emerged, that could be assigned to two main molecular programs: transcription/translation (pSHHt, pWNT and pGroup3myc), and synapses/immunological processes (pSHHs, pGroup3 and pGroup4). Multiomic analysis revealed different conservation levels of proteome features across MB subtypes at the DNA methylome level. Aggressive pGroup3myc MBs and favourable pWNT MBs were most similar in cluster hierarchies concerning overall proteome patterns but showed different protein abundances of the vincristine resistance-associated multiprotein complex TriC/CCT and of N-glycan turnover-associated factors. The N-glycome reflected proteome subtypes and complex-bisecting N-glycans characterized pGroup3myc tumors. Our results shed light on new targetable alterations in MB and set a foundation for potential immunotherapies targeting glycan structures.


Amino acid profiling is reported in the current study MTBLS9836.

Metabolite profiling is reported in MTBLS9830.

INSTRUMENT(S): Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Antonia Gocke 

PROVIDER: MTBLS9836 | MetaboLights | 2024-05-30

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
MTBLS9836 Other
FILES Other
a_MTBLS9836_LC-MS_positive_reverse-phase_metabolite_profiling.txt Txt
i_Investigation.txt Txt
m_MTBLS9836_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv Tabular
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