OSCR

Comprehensive proteogenomic characterization reveals clinically relevant molecular subtypes associated with medulloblastoma progression.

Overview

Authors: Seong-Min Park1, Kyung-Hee Kim1,2,3, Jong Hyuk Yoon4, Fulvio D’Angelo5, Seung Ah Choi6, Chan Il Kim1, Harim Koo7, Seungmin Park1, Hyondeog Kim1, Sreeja Sundara Raj1, Sung Soo Kim1, Ae Kyung Park8, Eun Jung Koh6,9, Seong-Ik Kim10, Yu-Mi Shim10, Lee Kwang-Hoon10, Eric Eunshik Kim10, Ji Hoon Phi6,9, Yeon Suk Jo3,11, Do Hyun Nam12
and 18 other authorsDaehee Hwang13, Do Young Hyeon13, Sunghyun Huh13, Hyung Joon Kwon1, Seokjun Ha1, Sanha Park1, Hyeji Shin1, Jeong Taik Kwon14, Heon Yoo15, Ho-Shin Gwak15, Michael D Taylor16,17,18,19,20,21,22,23,24,25, Bong Jin Park26, Jason K Sa27,28, Youngwook Kim1, Antonio Iavarone5,29, Sung-Hye Park10,30, Seung-Ki Kim6,9, Jong Bae Park1,31
ORCID iDs: Jong Hyuk Yoon, Fulvio D’Angelo, Harim Koo, Sung Soo Kim, Lee Kwang-Hoon, Do Hyun Nam, Daehee Hwang, Do Young Hyeon, Jason K Sa, Youngwook Kim, Antonio Iavarone, Sung-Hye Park
31 affiliations
  1. Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi Republic of Korea
  2. Proteomics Core Facility, Research Core Center, Research Institute, National Cancer Center, Goyang, Gyeonggi Republic of Korea
  3. Department of Applied Chemistry, School of Science and Technology, Kookmin University, Seoul, Republic of Korea
  4. Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu, Republic of Korea
  5. Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL USA
  6. Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children’s Hospital, Seoul, Republic of Korea
  7. Department of Medical Science Convergence, Graduate School of Medical Science, University of Ulsan, Ulsan, Korea
  8. Department of Pharmacy, School of Pharmacy and Institute of New Drug Development, Jeonbuk National University, Jeonju, Republic of Korea
  9. Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
  10. Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
  11. Department of Brain-Cognitive Science, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea
  12. AIMEDBIO, Songpa-gu, Seoul, Republic of Korea
  13. School of Biological Sciences, Seoul National University, Seoul, Republic of Korea
  14. Department of Neurosurgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
  15. Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea
  16. The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario Canada
  17. Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario Canada
  18. Department of Medical Biophysics, University of Toronto, Toronto, Ontario Canada
  19. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario Canada
  20. Texas Children’s Cancer and Hematology Center, Houston, TX USA
  21. Department of Pediatrics — Hematology/Oncology, Baylor College of Medicine, Houston, TX USA
  22. Department of Neurosurgery, Baylor College of Medicine, Houston, TX USA
  23. Department of Neurosurgery, Texas Children’s Hospital, Houston, TX USA
  24. Department of Surgery, University of Toronto, Toronto, Ontario Canada
  25. Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX USA
  26. Department of Neurosurgery, Kyung Hee University College of Medicine, Seoul, Republic of Korea
  27. Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea
  28. Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
  29. Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL USA
  30. Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
  31. Center for Multi-omics, Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, Republic of Korea
Institutions: Seoul National University (South Korea); Seoul National University Hospital (South Korea); National Cancer Center (South Korea); Korea Brain Research Institute (South Korea); University of Miami (United States); Sylvester Comprehensive Cancer Center (United States); Seoul National University Children's Hospital (South Korea); University of Ulsan (South Korea); Jeonbuk National University (South Korea); Kookmin University (South Korea); Daegu Gyeongbuk Institute of Science and Technology (South Korea); National Cancer Center Hospital (South Korea); Baylor College of Medicine (United States); University of Toronto (Canada); Hospital for Sick Children (Canada); Texas Children's Hospital (United States); Dan L Duncan Comprehensive Cancer Center; Korea University (South Korea)
Journal: Experimental & molecular medicine, volume 58, issue 6, pages 1885-1899
Dates: received 1 December 2025; accepted 8 March 2026; published online 5 June 2026; in print June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s12276-026-01732-0 · PMID 42249086 · PMCID PMC13323399 · OpenAlex W7163663913
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), other condition (population), cellular / molecular (subfield)
Keywords: Cancer microenvironment, Inflammation, Cancer metabolism, Autophagy
MeSH: Cerebellar Neoplasms*, Medulloblastoma*, Proteogenomics*, Animals, Cell Differentiation, Disease Progression, Hedgehog Proteins, Humans, Proteome, Proteomics (* major topic)
Topic: Hedgehog Signaling Pathway Studies (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Cancer Center (NCC) (NCC-1810861); National Research Foundation of Korea (2021R1A2C301331511)
Citations: not cited yet (Europe PMC); 21 references in the paper

Abstract

Current treatment strategies for medulloblastoma remain ineffective owing to extensive tumor heterogeneity. We generated five platforms of omics data including liquid chromatography and mass spectrometry-based proteome and performed integrated multi-omic characterization to improve the conventional molecular classification of medulloblastoma. We identified seven refined distinct subtypes. The sonic hedgehog (SHH) group was reclassified into two subgroups, SHHα and SHHβ, whereas group 4 was divided into three subgroups, G4α, G4β, and G4γ. SHH and group 4 subtypes exhibit two distinct neuronal differentiation trajectories: granular neuron and unipolar brush cell differentiation (SHHβ and G4γ, respectively), both of which associated with more favorable clinical outcomes. Furthermore, we uncovered unique proteomic and kinomic properties that conferred increased treatment vulnerabilities to targeted therapeutic interventions against each of the three medulloblastoma subtypes associated with poor clinical outcomes. We demonstrated the therapeutic potential of exploiting these vulnerabilities by utilizing a proteasome inhibitor and subtype-specific agents, including CDK1/2, PARP, CLK1, and MET inhibitors. Mechanistic insights were further elucidated through in-depth proteome analyses. Our study qualifies the use of proteomic signatures and activation of neuronal differentiation trajectories to tailor selective therapeutic opportunities for distinct subgroups of patients with medulloblastoma.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Other data links

Data availability

Raw omics data have been deposited in public repositories. Proteomic data have been deposited in the Proteomic Data Commons (PDC, https://proteomic.datacommons.cancer.gov/pdc/edu/; ID PDC000522, PDC000523, PDC000524, and PDC000525). DNA methylation idat files have been deposited to the Gene Expression Omnibus (GEO; ID GSE209668 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE209668)). Raw sequencing (fastq) files have been deposited into the SRA database (https://www.ncbi.nlm.nih.gov/sra) under project ID PRJNA862984, PRJNA863327, PRJNA864070, and PRJNA865394.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 38 authors, 4 keywords, 10 MeSH terms, 2 funders, 21 references.

Cite

This paper

Park, S.-M., Kim, K.-H., Yoon, J. H., D’Angelo, F., Choi, S. A., Kim, C. I., Koo, H., Park, S., Kim, H., Sundara Raj, S., Kim, S. S., Park, A. K., Koh, E. J., Kim, S.-I., Shim, Y.-M., Kwang-Hoon, L., Kim, E. E., Phi, J. H., Jo, Y. S., . . . Park, J. B. (2026). Comprehensive proteogenomic characterization reveals clinically relevant molecular subtypes associated with medulloblastoma progression. Experimental & molecular medicine, 58(6), 1885-1899. https://doi.org/10.1038/s12276-026-01732-0

BibTeX

@article{park2026comprehensive,
author = {Park, Seong-Min and Kim, Kyung-Hee and Yoon, Jong Hyuk and D’Angelo, Fulvio and Choi, Seung Ah and Kim, Chan Il and Koo, Harim and Park, Seungmin and Kim, Hyondeog and Sundara Raj, Sreeja and Kim, Sung Soo and Park, Ae Kyung and Koh, Eun Jung and Kim, Seong-Ik and Shim, Yu-Mi and Kwang-Hoon, Lee and Kim, Eric Eunshik and Phi, Ji Hoon and Jo, Yeon Suk and Nam, Do Hyun and Hwang, Daehee and Hyeon, Do Young and Huh, Sunghyun and Kwon, Hyung Joon and Ha, Seokjun and Park, Sanha and Shin, Hyeji and Kwon, Jeong Taik and Yoo, Heon and Gwak, Ho-Shin and D Taylor, Michael and Park, Bong Jin and Sa, Jason K and Kim, Youngwook and Iavarone, Antonio and Park, Sung-Hye and Kim, Seung-Ki and Park, Jong Bae},
title = {{Comprehensive proteogenomic characterization reveals clinically relevant molecular subtypes associated with medulloblastoma progression}},
journal = {Experimental \& molecular medicine},
year = {2026},
month = jun,
volume = {58},
number = {6},
pages = {1885--1899},
publisher = {Korean Society for Biochemistry and Molecular Biology},
issn = {1226-3613},
doi = {10.1038/s12276-026-01732-0},
url = {https://doi.org/10.1038/s12276-026-01732-0},
pmid = {42249086},
pmcid = {PMC13323399}
}

RIS

TY - JOUR
AU - Park, Seong-Min
AU - Kim, Kyung-Hee
AU - Yoon, Jong Hyuk
AU - D’Angelo, Fulvio
AU - Choi, Seung Ah
AU - Kim, Chan Il
AU - Koo, Harim
AU - Park, Seungmin
AU - Kim, Hyondeog
AU - Sundara Raj, Sreeja
AU - Kim, Sung Soo
AU - Park, Ae Kyung
AU - Koh, Eun Jung
AU - Kim, Seong-Ik
AU - Shim, Yu-Mi
AU - Kwang-Hoon, Lee
AU - Kim, Eric Eunshik
AU - Phi, Ji Hoon
AU - Jo, Yeon Suk
AU - Nam, Do Hyun
AU - Hwang, Daehee
AU - Hyeon, Do Young
AU - Huh, Sunghyun
AU - Kwon, Hyung Joon
AU - Ha, Seokjun
AU - Park, Sanha
AU - Shin, Hyeji
AU - Kwon, Jeong Taik
AU - Yoo, Heon
AU - Gwak, Ho-Shin
AU - D Taylor, Michael
AU - Park, Bong Jin
AU - Sa, Jason K
AU - Kim, Youngwook
AU - Iavarone, Antonio
AU - Park, Sung-Hye
AU - Kim, Seung-Ki
AU - Park, Jong Bae
TI - Comprehensive proteogenomic characterization reveals clinically relevant molecular subtypes associated with medulloblastoma progression
T2 - Experimental & molecular medicine
J2 - Exp Mol Med
PY - 2026
DA - 2026/06/05
VL - 58
IS - 6
SP - 1885
EP - 1899
SN - 1226-3613
PB - Korean Society for Biochemistry and Molecular Biology
DO - 10.1038/s12276-026-01732-0
UR - https://doi.org/10.1038/s12276-026-01732-0
LA - en
ER -

CSL-JSON

{
"id": "10.1038/s12276-026-01732-0",
"type": "article-journal",
"title": "Comprehensive proteogenomic characterization reveals clinically relevant molecular subtypes associated with medulloblastoma progression",
"container-title": "Experimental & molecular medicine",
"author": [
{
"family": "Park",
"given": "Seong-Min"
},
{
"family": "Kim",
"given": "Kyung-Hee"
},
{
"family": "Yoon",
"given": "Jong Hyuk"
},
{
"family": "D’Angelo",
"given": "Fulvio"
},
{
"family": "Choi",
"given": "Seung Ah"
},
{
"family": "Kim",
"given": "Chan Il"
},
{
"family": "Koo",
"given": "Harim"
},
{
"family": "Park",
"given": "Seungmin"
},
{
"family": "Kim",
"given": "Hyondeog"
},
{
"family": "Sundara Raj",
"given": "Sreeja"
},
{
"family": "Kim",
"given": "Sung Soo"
},
{
"family": "Park",
"given": "Ae Kyung"
},
{
"family": "Koh",
"given": "Eun Jung"
},
{
"family": "Kim",
"given": "Seong-Ik"
},
{
"family": "Shim",
"given": "Yu-Mi"
},
{
"family": "Kwang-Hoon",
"given": "Lee"
},
{
"family": "Kim",
"given": "Eric Eunshik"
},
{
"family": "Phi",
"given": "Ji Hoon"
},
{
"family": "Jo",
"given": "Yeon Suk"
},
{
"family": "Nam",
"given": "Do Hyun"
},
{
"family": "Hwang",
"given": "Daehee"
},
{
"family": "Hyeon",
"given": "Do Young"
},
{
"family": "Huh",
"given": "Sunghyun"
},
{
"family": "Kwon",
"given": "Hyung Joon"
},
{
"family": "Ha",
"given": "Seokjun"
},
{
"family": "Park",
"given": "Sanha"
},
{
"family": "Shin",
"given": "Hyeji"
},
{
"family": "Kwon",
"given": "Jeong Taik"
},
{
"family": "Yoo",
"given": "Heon"
},
{
"family": "Gwak",
"given": "Ho-Shin"
},
{
"family": "D Taylor",
"given": "Michael"
},
{
"family": "Park",
"given": "Bong Jin"
},
{
"family": "Sa",
"given": "Jason K"
},
{
"family": "Kim",
"given": "Youngwook"
},
{
"family": "Iavarone",
"given": "Antonio"
},
{
"family": "Park",
"given": "Sung-Hye"
},
{
"family": "Kim",
"given": "Seung-Ki"
},
{
"family": "Park",
"given": "Jong Bae"
}
],
"container-title-short": "Exp Mol Med",
"volume": "58",
"issue": "6",
"page": "1885-1899",
"DOI": "10.1038/s12276-026-01732-0",
"PMID": "42249086",
"PMCID": "PMC13323399",
"ISSN": "1226-3613",
"publisher": "Korean Society for Biochemistry and Molecular Biology",
"URL": "https://doi.org/10.1038/s12276-026-01732-0",
"language": "en",
"issued": {
"date-parts": [
[
2026,
6,
5
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.7150/ijbs.116040
Elucidating Tumorigenesis Mechanisms and Assessing Immunotherapeutic Efficacy in Patient-Derived Medulloblastoma Organoid Models.
Journal: International journal of biological sciences
In common: NCBI GEO GSE85217, genetics / omics, other condition, 4 references
[2] doi:10.1038/s41586-026-10612-6 [code]
Acquired genetic and cell-state changes in IDH-mutant glioma progression.
Journal: Nature
In common: other condition, cellular / molecular, 2 authors
[3] doi:10.1172/jci196753 [code]
Protein phosphatase 2A regulates senescence and immunogenicity in medulloblastoma models.
Journal: The Journal of clinical investigation
In common: NCBI GEO GSE85217, other condition, cellular / molecular, 2 references
[4] doi:10.3390/cells15050474
Longitudinal Detection of Tumor-Specific Peptides in Cerebrospinal Fluid for Pediatric Brain Tumor Surveillance.
Journal: Cells
In common: genetics / omics, other condition, 4 references
[5] doi:10.1111/bpa.70092
Molecular and clinical features of a Japanese medulloblastoma cohort: Subgroup-specific prognostic stratification using economical/accessible diagnostic methods.
Journal: Brain pathology (Zurich, Switzerland)
In common: genetics / omics, other condition, 4 references
[6] doi:10.1093/neuonc/noag053
ONC206 demonstrates potent antitumorigenic activity and is a potential novel therapeutic strategy for high-risk medulloblastoma.
Journal: Neuro-oncology
In common: NCBI GEO GSE85217, other condition
[7] doi:10.1038/s41467-026-76161-8
The m⁶A reader YTHDF2 regulates mRNA transport and axon outgrowth in developing neurons.
Journal: Nature communications
In common: author Jong Hyuk Yoon
[8] doi:10.1007/s12017-026-08935-8
Subgroup-Specific Associations of GRIA Genes Encoding AMPA Glutamate Receptor Subunits with Patient Survival in Medulloblastoma.
Journal: Neuromolecular medicine
In common: genetics / omics, other condition, cellular / molecular, 2 references
[9] doi:10.1113/jp289326
Maternal obesity induces activator protein 1-mediated inflammatory response to impair embryonic neurogenesis.
Journal: The Journal of physiology
In common: genetics / omics, other condition, 1 reference
[10] doi:10.1016/j.clinsp.2026.101003
Identification of metabolism-associated molecular classification and prognostic genes for medulloblastoma based on bioinformatics analysis.
Journal: Clinics (Sao Paulo, Brazil)
In common: genetics / omics, other condition, cellular / molecular, 1 reference

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.