PXD019046-1

PXD019046 is an original dataset announced via ProteomeXchange.

Title	Hotspot SF3B1 mutations determine response to PARP inhibitors
Description	Hotspot mutations in the spliceosomal component gene SF3B1 underpin a number of cancers and have a neomorphic function leading to global disruption of canonical splicing and aberrant splicing of hundreds of transcripts. However, the functional consequences of this misplicing and resultant genetic vulnerabilities imposed by these events are poorly understood. Through a synthetic-lethal approach we identify that SF3B1 mutant cells are selectively sensitive to PARP inhibitors. This vulnerability is preserved across multiple cell line and patent derived tumour models, independent of SF3B1 hotspot mutation and is manifested both in vitro and in vivo. These data provide the pre-clinical and mechanistic rationale for assessing SF3B1 mutations as a biomarker of single-agent PARP inhibitor response in a new patient population and may extend the clinical utility of these agents beyond BRCA mutated cancers.​
HostingRepository	PRIDE
AnnounceDate	2023-04-19
AnnouncementXML	Submission_2023-04-19_03:46:23.732.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JamesWright
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-07 22:29:48	ID requested
⏵ 1	2023-04-19 03:46:24	announced
2	2024-10-22 05:44:50	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human, SF3B1, MS3, TMT, Cancer, PARP inhibitors

JyotiChoudhary
contact affiliation	The Institute of Cancer Research
contact email	jyoti.choudhary@icr.ac.uk
lab head
JamesWright
contact affiliation	The Institute of Cancer Research
contact email	james.wright@icr.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019046
     1. Label: PRIDE project
     2. Name: Hotspot SF3B1 mutations determine response to PARP inhibitors