PXD031711

PXD031711 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics of truncated FGFR2, a clinically actionable oncogene in multiple cancers
Description	Somatic hotspot mutations and structural amplifications and fusions affecting fibroblast growth factor receptor 2 (FGFR2) occur in multiple cancer types. However, clinical responses to FGFR inhibitors (FGFRi) have remained variable, emphasizing a need to better understand which FGFR2 alterations are oncogenic and targetable. Here we applied transposon-based screening and tumor modelling in mice to uncover truncation of exon (E) 18 of Fgfr2 as a potent driver mutation. Human oncogenomic datasets revealed a diverse set of FGFR2 alterations, including rearrangements (REs), E1-E17 partial amplifications, and E18 nonsense and frameshift mutations, each causing transcription of E18-truncated FGFR2 (FGFR2deltaE18). Somatic modelling in mice and human tumor cell lines using a compendium of FGFR2deltaE18 and full-length variants identified FGFR2deltaE18-truncation as potent single-driver alteration in cancer. Here we show the phosphoproteomic landscape of FGFR2 variants in murine epithelial cell (MEC) lines and mouse tumors. Global (STY) phosphoproteomics using IMAC and phosphotyrosine phosphoproteomics using pTyr IP’s are combined with DIA protein expression data to uncover oncogenic signaling of clinically-relevant FGFR2 variants.
HostingRepository	PRIDE
AnnounceDate	2022-06-06
AnnouncementXML	Submission_2022-06-06_08:05:01.403.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sander Piersma
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-16 03:41:43	ID requested
⏵ 1	2022-06-06 08:05:01	announced

Dataset with its publication pending

submitter keyword: Mouse model, FGFR2, cancer, label-free, phosphoproteomics, IMAC, pTyrIP

Connie Jimenez
contact affiliation	AmsterdamUMC, Vrije Universiteit Amsterdam, Medical Oncology, Cancer Center Amsterdam, OncoProteomics Laboratory, Amsterdam, The Netherlands
contact email	c.jimenez@amsterdamumc.nl
lab head
Sander Piersma
contact affiliation	Amsterdam UMC
contact email	s.piersma@amsterdamumc.nl
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/2022/06/PXD031711

PRIDE project URI

• PRIDE
  1. PXD031711
     1. Label: PRIDE project
     2. Name: Phosphoproteomics of truncated FGFR2, a clinically actionable oncogene in multiple cancers