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

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Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level. / Godbole, Shweta; 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; Schüller, Ulrich; Krisp, Christoph; Neumann, Julia E.

In: NAT COMMUN, Vol. 15, No. 1, 24.07.2024, p. 6237.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Godbole, S, Voß, H, Gocke, A, Schlumbohm, S, Schumann, Y, Peng, B, Mynarek, M, Rutkowski, S, Dottermusch, M, Dorostkar, MM, Korshunov, A, Mair, T, Pfister, SM, Kwiatkowski, M, Hotze, M, Neumann, P, Hartmann, C, Weis, J, Liesche-Starnecker, F, Guan, Y, Moritz, M, Siebels, B, Struve, N, Schlüter, H, Schüller, U, Krisp, C & Neumann, JE 2024, 'Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level', NAT COMMUN, vol. 15, no. 1, pp. 6237. https://doi.org/10.1038/s41467-024-50554-z

APA

Godbole, S., Voß, H., Gocke, A., Schlumbohm, S., Schumann, Y., Peng, B., Mynarek, M., Rutkowski, S., Dottermusch, M., Dorostkar, M. M., Korshunov, A., Mair, T., Pfister, S. M., Kwiatkowski, M., Hotze, M., Neumann, P., Hartmann, C., Weis, J., Liesche-Starnecker, F., ... Neumann, J. E. (2024). Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level. NAT COMMUN, 15(1), 6237. https://doi.org/10.1038/s41467-024-50554-z

Vancouver

Godbole S, Voß H, Gocke A, Schlumbohm S, Schumann Y, Peng B et al. Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level. NAT COMMUN. 2024 Jul 24;15(1):6237. https://doi.org/10.1038/s41467-024-50554-z

Bibtex

@article{9c42a33da63f4e34840aa00796f45752,
title = "Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level",
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, Humans, Polysaccharides/metabolism, Proteome/metabolism, Cerebellar Neoplasms/metabolism, DNA Methylation, Transcriptome, Child, Proteomics/methods, Female, Gene Expression Regulation, Neoplastic, Male, Child, Preschool, Gene Expression Profiling/methods",
author = "Shweta Godbole and Hannah Vo{\ss} and Antonia Gocke and Simon Schlumbohm and Yannis Schumann and Bojia Peng and Martin Mynarek and Stefan Rutkowski and Matthias Dottermusch and Dorostkar, {Mario M} and Andrey Korshunov and Thomas Mair and Pfister, {Stefan M} and Marcel Kwiatkowski and Madlen Hotze and Philipp Neumann and Christian Hartmann and Joachim Weis and Friederike Liesche-Starnecker and Yudong Guan and Manuela Moritz and Bente Siebels and Nina Struve and Hartmut Schl{\"u}ter and Ulrich Sch{\"u}ller and Christoph Krisp and Neumann, {Julia E}",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = jul,
day = "24",
doi = "10.1038/s41467-024-50554-z",
language = "English",
volume = "15",
pages = "6237",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level

AU - Godbole, Shweta

AU - Voß, Hannah

AU - Gocke, Antonia

AU - Schlumbohm, Simon

AU - Schumann, Yannis

AU - Peng, Bojia

AU - Mynarek, Martin

AU - Rutkowski, Stefan

AU - Dottermusch, Matthias

AU - Dorostkar, Mario M

AU - Korshunov, Andrey

AU - Mair, Thomas

AU - Pfister, Stefan M

AU - Kwiatkowski, Marcel

AU - Hotze, Madlen

AU - Neumann, Philipp

AU - Hartmann, Christian

AU - Weis, Joachim

AU - Liesche-Starnecker, Friederike

AU - Guan, Yudong

AU - Moritz, Manuela

AU - Siebels, Bente

AU - Struve, Nina

AU - Schlüter, Hartmut

AU - Schüller, Ulrich

AU - Krisp, Christoph

AU - Neumann, Julia E

N1 - © 2024. The Author(s).

PY - 2024/7/24

Y1 - 2024/7/24

N2 - 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.

AB - 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.

KW - Medulloblastoma/metabolism

KW - Humans

KW - Polysaccharides/metabolism

KW - Proteome/metabolism

KW - Cerebellar Neoplasms/metabolism

KW - DNA Methylation

KW - Transcriptome

KW - Child

KW - Proteomics/methods

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Male

KW - Child, Preschool

KW - Gene Expression Profiling/methods

U2 - 10.1038/s41467-024-50554-z

DO - 10.1038/s41467-024-50554-z

M3 - SCORING: Journal article

C2 - 39043693

VL - 15

SP - 6237

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -