{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chan PY"],"funding":["RCUK | Biotechnology and Biological Sciences Research Council","Wellcome Trust","Center for Strategic Scientific Initiatives, National Cancer Institute","Biotechnology and Biological Sciences Research Council","CSRD VA"],"pagination":["1672-1683"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12283370"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["57(7)"],"pubmed_abstract":["Metastatic 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. Analysis involved genome-wide single-gene and combinatorial paired-gene CRISPR libraries. Among our 76 uveal melanoma-specific essential genes and 105 synthetic lethal gene pairs, we identified and validated the CDP-diacylglycerol synthase 2 gene (CDS2) as a genetic dependency in the context of low CDP-diacylglycerol synthase 1 gene (CDS1) expression. We further demonstrate that CDS1/CDS2 forms a synthetic lethal interaction in vivo and reveal that CDS2 knockout results in the disruption of phosphoinositide synthesis and increased cellula"],"journal":["Nature genetics"],"pubmed_title":["The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types."],"pmcid":["PMC12283370"],"funding_grant_id":["1","220540/Z/20/A","BB/T002530/1","BB/Y006925/1"],"pubmed_authors":["Woods M","Raimondi F","Stephens L","Vinceti A","Thompson NA","Wessels L","Mehta I","Hawkins PT","van de Haar J","Bisceglia L","Adams DJ","Alexander D","Goncalves E","Harle V","Kozik Z","Del Castillo Velasco-Herrera M","Iyer V","Wong K","Patiyal S","Matsuyama LSAS","Olvera-Leon R","Vazquez-Cruz ME","Balmus G","Arriaga-Gonzalez FG","Park JS","van der Weyden L","Offord V","Iorio F","Ryan CJ","Sinha S","Chan PY","Choudhary J","Venkatesh A","Barneda D","Cheema S"],"additional_accession":[]},"is_claimable":false,"name":"The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types.","description":"Metastatic 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. Analysis involved genome-wide single-gene and combinatorial paired-gene CRISPR libraries. Among our 76 uveal melanoma-specific essential genes and 105 synthetic lethal gene pairs, we identified and validated the CDP-diacylglycerol synthase 2 gene (CDS2) as a genetic dependency in the context of low CDP-diacylglycerol synthase 1 gene (CDS1) expression. We further demonstrate that CDS1/CDS2 forms a synthetic lethal interaction in vivo and reveal that CDS2 knockout results in the disruption of phosphoinositide synthesis and increased cellula","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-07-15T06:53:21.162Z","creation":"2025-08-16T03:06:08.835Z"},"accession":"S-EPMC12283370","cross_references":{"pubmed":["40615675"],"doi":["10.1038/s41588-025-02222-1"]}}