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PXD053752

PXD053752 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting the CDS1/2 axis as a therapeutic strategy in uveal melanoma and pan-cancer
DescriptionMetastatic uveal melanoma is an aggressive disease with limited effective therapeutic options. To comprehensively map monogenic and digenic dependencies, we performed CRISPR-Cas9 screening in ten extensively profiled human uveal melanoma cell line models using genome-wide single gene/gRNA and combinatorial paired gene/paired gRNA CRISPR libraries. Within our identified uveal melanoma-specific essential genes and synthetic lethal gene pairs, we identified and validated CDS2 as a novel genetic dependency in the context of low CDS1 expression. We further demonstrate that CDS1/CDS2 is a synthetic lethal interaction in vivo and reveal that CDS2 knockout results in the disruption of phosphoinositide synthesis, cellular apoptosis, and that re-expression of CDS1 rescues the cell fitness defect provoked by CDS2 loss. We extend our analysis using pan-cancer data confirming increased CDS2 essentiality in diverse tumour types with low CDS1 expression. Our results suggest that CDS2 inhibition should be investigated as a therapeutic strategy in uveal melanoma that may extend to multiple tumour types with low CDS1 expression. The data provided in this dataset explore the effect of CDS2 loss in uveal melanoma cell lines.
HostingRepositoryPRIDE
AnnounceDate2025-04-01
AnnouncementXMLSubmission_2025-04-01_04:13:47.902.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGraeme Benstead-Hume
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Ascend
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-08 05:24:05ID requested
12025-04-01 04:13:48announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: CDS1, , CDS2, uveal melanom
Contact List
Jyoti Choudhary
contact affiliationFunctional Proteomics, ICR
contact emailjyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliationICR
contact emailghume@icr.ac.uk
dataset submitter
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Dataset FTP location
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