PXD016828 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteogenomics analysis unveils a novel TFG-RET gene fusion and druggable targets in papillary thyroid carcinomas |
Description | Papillary thyroid cancer (PTC) is the most common type of endocrine malignancy. From a set of PTC patients whose tumor did not harbour any BRAF or RAS mutations, a 35 years old male patient’s normal, primary tumor and lymph node (LN) metastatic tissues were subjected to genomics and proteomics analysis. By RNA-seq analysis, we identified a novel RET rearrangement involving exons 1-4 from the 5’ end of the Trk fused Gene (TFG) fused to the 3’ end of RET tyrosine kinase leading to a TFG-RET fusion which transforms immortalized human thyroid cells in a kinase-dependent manner. Further, TFG-RET oncogene oligomerises in a PB1 domain-dependent manner and consistently, mutation of the oligomerisation interface led to the inhibition of RET-mediated oncogenic transformation. Quantitative proteomic analysis of the same samples revealed the upregulation of proteins involved in the ubiquitination machinery including E3 Ubiquitin ligase HUWE1 and DUBs like USP9X and UBP7 in both tumor and LN metastatic lesions. We further identified that expression of TFG-RET led to the upregulation of HUWE1. Further, in a cohort of PTC patients, we observed higher expression of HUWE1, USP9X and USP7 in the tumor and metastatic lesions, when compared to the matched normal tissue. Transient knockdown of HUWE1, USP9X and USP7 affected viability and proliferation of TFG-RET transformed cells. Consistently, inhibition of RET, HUWE1 and DUBs by small molecule inhibitors significantly reduced RET-mediated oncogenesis. Apart from unveiling a novel oncogenic RET fusion in PTCs, our data may open a novel avenue of targeting ubiquitin signaling machinery in human PTCs. |
HostingRepository | PRIDE |
AnnounceDate | 2020-04-02 |
AnnouncementXML | Submission_2020-06-12_04:32:35.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Bernd Thiede |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-12-19 05:25:19 | ID requested | |
1 | 2020-04-01 22:23:09 | announced | |
⏵ 2 | 2020-06-12 04:32:36 | announced | 2020-06-12: Updated publication reference for PubMed record(s): 32345963. |
Publication List
Krishnan A, Berthelet J, Renaud E, Rosigkeit S, Distler U, Stawiski E, Wang J, Modrusan Z, Fiedler M, Bienz M, Tenzer S, Schad A, Roth W, Thiede B, Seshagiri S, Musholt TJ, Rajalingam K, Proteogenomics analysis unveils a TFG-RET gene fusion and druggable targets in papillary thyroid carcinomas. Nat Commun, 11(1):2056(2020) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: PTC/ RET/ HUWE1/ USP7/ USP9X / Precision medicine/ TFG-RET |
Contact List
Bernd Thiede |
contact affiliation | Proteomics Core facility, Department of Biosciences, University of Oslo, Norway |
contact email | bernd.thiede@ibv.uio.no |
lab head | |
Bernd Thiede |
contact affiliation | University of Oslo |
contact email | bernd.thiede@ibv.uio.no |
dataset submitter | |
Full Dataset Link List
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/2020/04/PXD016828 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD016828
- Label: PRIDE project
- Name: Proteogenomics analysis unveils a novel TFG-RET gene fusion and druggable targets in papillary thyroid carcinomas