PXD045522-1

PXD045522 is an original dataset announced via ProteomeXchange.

Title	Multi-Omic and Functional Analysis for Classification and Treatment of Sarcomas with FUS-TFCP2 or EWSR1-TFCP2 Fusions
Description	Linking clinical multi-omics analyses with mechanistic studies may improve the understanding of rare cancers. We leveraged two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibited outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing. This resulted in the expression of ALK variants, i.e. short transcripts (ST), which we named ALK-ST1 (consisting of exons 1-2:18–29), ALK-ST2 (1:18–29), ALK-ST3 (18–29), and ALK-ST4 (1–5:12–17). To systematically investigate the oncogenic capacity of these ALK variants, we stably expressed them in p53-deficient MCF10A human mammary epithelial cells and performed different transformation assays. These experiments demonstrated that ALK-ST1, ALK-ST2, and ALK-ST3 are oncogenic variants, while ALK-ST4 could not transform MCF10A cells. We confirmed protein expression of ALK-ST1, ALK-ST2, and ALK-ST3 by western blotting, which was not possible for ALK-ST4 due to lack of a specific antibody that binds to the N-terminus of ALK that is lost in ALK-ST4. We therefore performed mass spectrometry-based label-free quantitative proteomics on lysates from MCF10A cells stably expressing empty vector (EV), wildtype ALK (ALK-WT), or ALK-ST4 to confirm its expression.
HostingRepository	PRIDE
AnnounceDate	2023-11-13
AnnouncementXML	Submission_2023-11-13_01:57:21.024.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ClaudiaScholl
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-20 07:51:35	ID requested
⏵ 1	2023-11-13 01:57:21	announced

Dataset with its publication pending

submitter keyword: ALK, FUS-TFCP2, sarcoma, EWSR1-TFCP2

ClaudiaScholl
contact affiliation	Division of Applied Functional Genomics, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), NCT Heidelberg, Germany
contact email	claudia.scholl@nct-heidelberg.de
lab head
ClaudiaScholl
contact affiliation	German Cancer Research Center (DKFZ)
contact email	claudia.scholl@nct-heidelberg.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/2023/11/PXD045522

PRIDE project URI

• PRIDE
  1. PXD045522
     1. Label: PRIDE project
     2. Name: Multi-Omic and Functional Analysis for Classification and Treatment of Sarcomas with FUS-TFCP2 or EWSR1-TFCP2 Fusions