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Molecular changes during AT/RT progression associated with epithelial-mesenchymal transition and extracellular matrix changes.

Overview

Authors: Lea Altendorf1,2, Anton Althammer1,2,3, Rajanya Roy4, Karoline Hack1,2, Flavia W. de Faria4, Arend Koch5, Vanessa Thaden1,2, Melanie Schoof1,2, Martin U. Schuhmann6, Peter Hauser7, Pascal D. Johann8,9,10, Martin Hasselblatt11, Michael C. Frühwald8, Kornelius Kerl4, Ulrich Schüller1,2,12
ORCID iDs: Ulrich Schüller
  1. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf,20251 Hamburg, Germany
  2. Research Institute Children’s Cancer Center Hamburg,Martinistraße 52, N63, 20251 Hamburg, Germany
  3. Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf,20251 Hamburg, Germany
  4. Department of Pediatric Hematology and Oncology, University Medical Center Münster,48149 Münster, Germany
  5. Institute of Neuropathology, Charité – Universitätsmedizin Berlin,10117 Berlin, Germany
  6. Division of Pediatric Neurosurgery, Department of Neurosurgery, Eberhard Karl’s University Hospital of Tübingen,72076 Tübingen, Germany
  7. Second Department of Pediatrics, Semmelweis University,1085 Budapest, Hungary
  8. Paediatric and Adolescent Medicine, Swabian Children’s Cancer Center Augsburg, EU-RHAB Trial Center, 86156 Augsburg, Germany
  9. Hopp Children’s Cancer Center (KiTZ), German Cancer Research Center (DKFZ) and German Cancer Research Consortium (DKTK),69120 Heidelberg, Germany
  10. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Research Consortium (DKTK),69120 Heidelberg, Germany
  11. Institute of Neuropathology, University Hospital Münster,48149 Münster, Germany
  12. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf,20251 Hamburg, Germany
Journal: Acta neuropathologica, volume 152, issue 1, article 1
Dates: received 29 December 2025; accepted 24 June 2026; published online 1 July 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1007/s00401-026-03050-1 · PMID 42384079 · PMCID PMC13323348 · OpenAlex W7166884439
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), histology / microscopy (modality), human (organism), other condition (population)
Methods: Statistics, Smoothing, state filtering, decompositions, Connectivity, Machine learning, fMRI & imaging
Keywords: AT/RT, Tumor recurrence, Therapy resistance, Single-nucleus RNA sequencing, pEMT
MeSH: Brain Neoplasms*, Epithelial-Mesenchymal Transition*, Extracellular Matrix*, Disease Progression, Female, Humans, Infant, Male, Neoplasm Recurrence, Local, Tumor Microenvironment (* major topic)
Topic: Chromatin Remodeling and Cancer (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Deutsche Forschungsgemeinschaft; Universitätsklinikum Hamburg-Eppendorf (UKE) (5411)
Citations: not cited yet (Europe PMC); 66 references in the paper
Research resources: RRID:AB_2148557, mouse anti-Langerin RRID:AB_2889342, mouse anti-CD1A RRID:AB_563515, CHLA-266 RRID:CVCL_M149, RRID:CVCL_M156, the adapters were trimmed with Skewer RRID:SCR_001151, Gene Ontology RRID:SCR_002811, All stainings were quantified in ImageJ RRID:SCR_003070, The Reactome Pathway RRID:SCR_003485, RRID:SCR_004463, g:Profiler RRID:SCR_006809, RRID:SCR_007322, RRID:SCR_014601, RRID:SCR_015058, The DESeq2 package RRID:SCR_015687, RRID:SCR_016418, RRID:SCR_016954, As the basis for the CIBERSORT analysis RRID:SCR_016955, RRID:SCR_017344, RRID:SCR_018931, ShinyGO RRID:SCR_019213, RRID:SCR_019214, RRID:SCR_019316, RRID:SCR_021084, RRID:SCR_021137, RRID:SCR_021140, RRID:SCR_021327, The databases PanglaoDB RRID:SCR_022580, the NMF package RRID:SCR_023124, RRID:SCR_025045, RRID:SCR_025250, RRID:SCR_025619, we utilized the R package miloR RRID:SCR_025630, RRID:SCR_025679, RRID:SCR_025968, RRID:SCR_026996

Abstract

Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors during infancy and associated with a dismal prognosis. The majority of patients suffer from tumor progression or recurrence, but underlying mechanisms remain unknown. To better understand such mechanisms, we performed single-nucleus RNA sequencing (snRNAseq) of eight paired primary tumors and recurrences. Tumor cells and cells of the tumor microenvironment (TME) were analyzed separately. Potentially therapy-resistant tumor cells were identified through the comparison of global gene expression profiles between primary and recurrent tumor cell populations using CIBERSORT. Histopathology, in vitro experiments, bulk RNA sequencing, and survival analysis were performed for validation. Paired primary and recurrent AT/RT showed significant differences in their gene expression profiles. Potentially therapy-resistant AT/RT-MYC tumor cells revealed changes in the extracellular matrix (ECM) as well as altered developmental processes and immune signaling pathways. Respective gene signatures were correlated with inferior survival in AT/RT-MYC patients. Tumor cells of relapsed AT/RT-MYC underwent partial epithelial–mesenchymal transition (pEMT), a feature that was confirmed by immunohistochemistry (IHC) and by analyzing AT/RT cells after standard therapy in vitro. Together, we identified potential mechanisms of tumor relapse and therapy resistance in AT/RT, which could be employed to improve therapy in future.

Supplementary Information: The online version contains supplementary material available at 10.1007/s00401-026-03050-1.

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.

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Data

Data links

Data availability

All generated data of this study are deposited at NCBI Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo). The snRNAseq data of paired primary and recurrent AT/RT are accessible through GEO Series accession number GSE298139. Bulk RNAseq data of AT/RT-MYC primary tumors were obtained from previous studies [28, 30] or were generated for this study. These data are accessible through GEO Series accession number GSE298140. Bulk RNAseq data of the untreated and treated AT/RT-MYC cell lines are accessible via GSE298141.

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 2, 28 September 2026

  • Publisher: n/a → Springer Science+Business Media

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 5 keywords, 10 MeSH terms, 2 funders, 56 references, 36 RRIDs.

Cite

This paper

Altendorf, L., Althammer, A., Roy, R., Hack, K., de Faria, F. W., Koch, A., Thaden, V., Schoof, M., Schuhmann, M. U., Hauser, P., Johann, P. D., Hasselblatt, M., Frühwald, M. C., Kerl, K., & Schüller, U. (2026). Molecular changes during AT/RT progression associated with epithelial-mesenchymal transition and extracellular matrix changes. Acta neuropathologica, 152(1), 1. https://doi.org/10.1007/s00401-026-03050-1

BibTeX

@article{altendorf2026molecular,
author = {Altendorf, Lea and Althammer, Anton and Roy, Rajanya and Hack, Karoline and de Faria, Flavia W. and Koch, Arend and Thaden, Vanessa and Schoof, Melanie and Schuhmann, Martin U. and Hauser, Peter and Johann, Pascal D. and Hasselblatt, Martin and Frühwald, Michael C. and Kerl, Kornelius and Schüller, Ulrich},
title = {{Molecular changes during AT/RT progression associated with epithelial-mesenchymal transition and extracellular matrix changes}},
journal = {Acta neuropathologica},
year = {2026},
month = jul,
volume = {152},
number = {1},
pages = {1},
publisher = {Springer Science+Business Media},
issn = {0001-6322},
doi = {10.1007/s00401-026-03050-1},
url = {https://doi.org/10.1007/s00401-026-03050-1},
pmid = {42384079},
pmcid = {PMC13323348}
}

RIS

TY - JOUR
AU - Altendorf, Lea
AU - Althammer, Anton
AU - Roy, Rajanya
AU - Hack, Karoline
AU - de Faria, Flavia W.
AU - Koch, Arend
AU - Thaden, Vanessa
AU - Schoof, Melanie
AU - Schuhmann, Martin U.
AU - Hauser, Peter
AU - Johann, Pascal D.
AU - Hasselblatt, Martin
AU - Frühwald, Michael C.
AU - Kerl, Kornelius
AU - Schüller, Ulrich
TI - Molecular changes during AT/RT progression associated with epithelial-mesenchymal transition and extracellular matrix changes
T2 - Acta neuropathologica
J2 - Acta Neuropathol
PY - 2026
DA - 2026/07/01
VL - 152
IS - 1
SP - 1
SN - 0001-6322
PB - Springer Science+Business Media
DO - 10.1007/s00401-026-03050-1
UR - https://doi.org/10.1007/s00401-026-03050-1
LA - en
ER -

CSL-JSON

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