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

Godbole, Shwera; Voß, Hannah; Gocke, Antonia; Schlumbohm, Simon; Schumann, Yannis; Peng, Bojia; Mynarek, Martin; Rutkowski, Stefan; Dottermusch, Matthias; Dorostkar, Mario M.; Korshunov, Andrey; Mair, Thomas; Pfister, Stefan M.; Kwiatkowski, Marcel; Hotze, Madlen; Neumann, Philipp; Hartmann, Christian; Weis, Joachim; Liesche-Starnecker, Friederike; Guan, Yudong; Moritz, Manuela; Siebels, Bente; Struve, Nina; Schlüter, Hartmut; Neumann, Julia

doi:10.1038/s41467-024-50554-z

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

Publication date

2024-07-24

Document type

Forschungsartikel

Author

Godbole, Shwera

Voß, Hannah

Gocke, Antonia

Schlumbohm, Simon

Schumann, Yannis

Peng, Bojia

Mynarek, Martin

Rutkowski, Stefan

Dottermusch, Matthias

Dorostkar, Mario M.

Korshunov, Andrey

Mair, Thomas

Pfister, Stefan M.

Kwiatkowski, Marcel

Hotze, Madlen

Neumann, Philipp

Hartmann, Christian

Weis, Joachim

Liesche-Starnecker, Friederike

Guan, Yudong

Moritz, Manuela

Siebels, Bente

Struve, Nina

Schlüter, Hartmut

Neumann, Julia

Organisational unit

High Performance Computing

DOI

10.1038/s41467-024-50554-z

URI

https://openhsu.ub.hsu-hh.de/handle/10.24405/16693

ISSN

2041-1723

Series or journal

Nature communications

Periodical volume

15

Peer-reviewed

✅

Part of the university bibliography

✅

DDC Class

004 Informatik

500 Naturwissenschaften

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.

Cite as

Godbole, S., Voß, H., Gocke, A. et al. Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level. Nat Commun 15, 6237 (2024). https://doi.org/10.1038/s41467-024-50554-z

Version

Published version

Access right on openHSU

Metadata only access

Options

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