PXD053786-1

PXD053786 is an original dataset announced via ProteomeXchange.

Title	Super-enhancer-driven CACNA2D2 is an EWSR1::WT1 signature gene encoding a diagnostic marker for desmoplastic small round cell tumor (DSRCT)
Description	Desmoplastic small round cell tumor (DSRCT) is a highly aggressive cancer predominantly occurring in young male adolescents. It mainly arises at sites lined by mesothelium, such as the abdominal cavity, and is driven by the pathognomonic EWSR1::WT1 fusion oncoprotein. The dismal survival rates (5–20%) have not significantly improved since its first description in 1989, also due to a lack of comprehensive datasets that could shed new light on the biology of the disease and uncover novel diagnostic markers and therapeutic targets. Thus, we established genome-wide single-cell RNA-sequencing and bulk proteomic data of in vitro and in vivo-generated EWSR1::WT1 knockdown models and combined them with an original systems-biology-based pipeline including patient data, resulting in a rich resource for discovery analyses. This approach revealed the alpha-2/delta subunit of the voltage-dependent calcium channel complex, CACNA2D2, as a strongly overexpressed direct target of EWSR1::WT1 in DSRCTs, which is regulated by an EWSR1::WT1-bound super-enhancer. Ectopic expression of the main EWSR1::WT1 isoforms in mesothelial cells, the putative cell of origin of DSRCTs, confirmed that EWSR1::WT1 is sufficient to induce super-enhancer formation at the CACNA2D2 locus followed by robust transcription of this gene. Moreover, single-cell and bulk-level analyses on patient samples and cell line-derived xenografts highlighted CACNA2D2 as a critical mediator of the EWSR1::WT1 oncogenic signature. Based on bulk and single-cell transcriptomic data, the computed CACNA2D2 signature could be further utilized to robustly identify DSRCTs in reference sets. Finally, we show that CACNA2D2 is a highly sensitive and specific single biomarker for fast, simple, and cost-efficient diagnosis of DSRCT. Collectively, we established a freely available large-scale multi-omics dataset for this devastating disease and provide a blueprint of how such data can be used to identify a new and clinically relevant diagnostic marker, which may significantly reduce misdiagnoses, and thus improve patient care.
HostingRepository	PRIDE
AnnounceDate	2025-06-30
AnnouncementXML	Submission_2025-06-29_16:33:49.273.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefanie Kutschmann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-09 01:14:57	ID requested
⏵ 1	2025-06-29 16:33:50	announced

10.1002/cac2.70015;

Geyer FH, Ritter A, Kinn-Gurzo S, Faehling T, Li J, Jarosch A, Ngo C, Vinca E, Aljakouch K, Orynbek A, Ohmura S, Kirchner T, Imle R, Romero-P, é, rez L, D, í, az-Mart, í, n J, Bertram S, de , Á, lava E, Henon C, Postel-Vilnay S, Banito A, Sill M, Versleijen-Jonkers Y, Mayer BFB, Ebinger M, Sparber-Sauer M, Stegmaier S, Baumhoer D, Hartmann W, Krijgsveld J, Horst D, Delattre O, Grohar PJ, Gr, ü, newald TGP, Cidre-Aranaz F, Comprehensive DSRCT multi-omics analyses unveil CACNA2D2 as a diagnostic hallmark and super-enhancer-driven EWSR1::WT1 signature gene. Cancer Commun (Lond), 45(6):702-708(2025) [pubmed]

submitter keyword: super-enhancer,DSRCT, proteomics, scRNA-seq, CACNA2D2, EWSR1::WT1, IHC, biomarker

Dr. Florencia Cidre-Aranaz
contact affiliation	Hopp Children`s Cancer Center Heidelberg (KiTZ) National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Germany Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
contact email	florencia.cidrearanaz@dkfz-heidelberg.de
lab head
Stefanie Kutschmann
contact affiliation	DKFZ (German Cancer Research Center) Division of Translational Pediatric Sarcoma Research (B410)
contact email	s.kutschmann@dkfz.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/06/PXD053786

PRIDE project URI

• PRIDE
  1. PXD053786
     1. Label: PRIDE project
     2. Name: Super-enhancer-driven CACNA2D2 is an EWSR1::WT1 signature gene encoding a diagnostic marker for desmoplastic small round cell tumor (DSRCT)