PXD045268

PXD045268 is an original dataset announced via ProteomeXchange.

Title	Integrated proteomics spotlight the proteasome as a pervasive therapeutic vulnerability in Embryonal Tumors with Multilayered Rosettes (ETMR)
Description	Embryonal tumors with multilayered rosettes (ETMR) are rare malignant embryonal brain tumors. The prognosis of ETMR is poor and novel therapeutic approaches are desperately needed. Comprehension of ETMR tumor biology is based on only few previous molecular studies, which mainly relied on the analyses of nucleic acids. In this study, we explored integrated ETMR proteomics with the aim to identify novel therapeutic vulnerabilities in these deadly tumors. Using mass spectrometry, proteome data were acquired from FFPE tissue of 40 embryonal brain tumors (16 ETMR, 9 atypical teratoid/rhabdoid tumors (AT/RT), 15 medulloblastomas (MB)) and integrated with case-matched global DNA methylation data, publicly available transcriptome data, and proteome data of further pediatric brain tumors. Proteome-based cluster analyses grouped ETMR samples according to histomorphology, separating neuropil-rich tumors with neuronal signatures from primitive tumors with signatures relating to stemness and chromosome organization. Microdissection analyses highlighted the close relationship of ETMR histomorphology and proteome profiles, regardless of intra- or intertumoral comparisons. Integrated proteomics showcased that ETMR harbor proteasome regulatory proteins in abundancy, implicating their strong dependency on the proteasome machinery to safeguard proteostasis. Respectively, in vitro cell culture viability assays using embryonal brain tumor cell lines BT183 (ETMR), BT16 (AT/RT), and D283 (MB) highlighted that ETMR cells were highly vulnerable towards treatment with the CNS penetrant proteasome inhibitor Marizomib. In summary, histomorphology stipulates the proteome signatures of ETMR. Pervasive and histomorphology-independent abundancy of proteasome regulatory proteins in ETMR indicates a strong proteasome dependency throughout these tumors. As validated in cell culture experiments, proteasome inhibition poses a promising therapeutic option in ETMR.
HostingRepository	PRIDE
AnnounceDate	2024-01-08
AnnouncementXML	Submission_2024-01-08_08:24:49.028.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ali Biabani
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-11 07:28:59	ID requested
⏵ 1	2024-01-08 08:24:49	announced

Dottermusch M, Biabani A, Lempertz T, Schumann Y, Navolic J, Godbole S, Obrecht D, Frank S, Dorostkar MM, Vo, ß H, Schl, ü, ter H, Rutkowski S, Sch, ü, ller U, Neumann JE, Integrated proteomics spotlight the proteasome as a therapeutic vulnerability in embryonal tumors with multilayered rosettes. Neuro Oncol, 26(5):935-949(2024) [pubmed]

10.1093/neuonc/noad265;

submitter keyword: transcriptome, multiomics,Embryonal Tumor with Multilayered Rosettes, mass spectrometry, 850K, methylome, ETMR, embryonal brain tumor, LIN28A, DNA methylation, proteome

Prof. Dr. Hartmut Schlüter
contact affiliation	Section mass-spectrometry and proteomics Diagnostic Center, Research Campus N27 Room 00.008 Martinistr. 52 20246 Hamburg
contact email	hschluet@uke.de
lab head
Ali Biabani
contact affiliation	University Medical Center Hamburg-Eppendorf
contact email	a.biabani@uke.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045268
     1. Label: PRIDE project
     2. Name: Integrated proteomics spotlight the proteasome as a pervasive therapeutic vulnerability in Embryonal Tumors with Multilayered Rosettes (ETMR)