{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Haider S"],"funding":["Cancer Research UK","Breast Cancer Now"],"pagination":["522-529"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11906352"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["57(3)"],"pubmed_abstract":["To maintain cell fitness, deleterious genetic alterations are buffered by compensatory changes in additional genes. In cancer, buffering processes could be targeted by synthetic lethality. However, despite the large-scale identification of synthetic lethal effects in preclinical models, evidence that these operate clinically is limited. This impedes the application of synthetic lethal approaches. By integrating molecular profiling data from >9,000 cancers with synthetic lethal screens, we show that transcriptomic buffering of tumor suppressor gene (TSG) loss by hyperexpression of synthetic lethal partners is a common phenomenon, extending to multiple TSGs and histotypes. Transcriptomic buffering is also notable in cancers that phenocopy TSG loss, such as BRCAness cancers, where expression "],"journal":["Nature genetics"],"pubmed_title":["The transcriptomic architecture of common cancers reflects synthetic lethal interactions."],"pmcid":["PMC11906352"],"funding_grant_id":["DRCRPGNov21y100001","CTR-Q5-Y5"],"pubmed_authors":["Pettitt SJ","Lord CJ","Brough R","Madera S","Haider S","Wicks A","Gulati A","Alexander J","Tutt ANJ","Iacovacci J"],"additional_accession":[]},"is_claimable":false,"name":"The transcriptomic architecture of common cancers reflects synthetic lethal interactions.","description":"To maintain cell fitness, deleterious genetic alterations are buffered by compensatory changes in additional genes. In cancer, buffering processes could be targeted by synthetic lethality. However, despite the large-scale identification of synthetic lethal effects in preclinical models, evidence that these operate clinically is limited. This impedes the application of synthetic lethal approaches. By integrating molecular profiling data from >9,000 cancers with synthetic lethal screens, we show that transcriptomic buffering of tumor suppressor gene (TSG) loss by hyperexpression of synthetic lethal partners is a common phenomenon, extending to multiple TSGs and histotypes. Transcriptomic buffering is also notable in cancers that phenocopy TSG loss, such as BRCAness cancers, where expression ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-06-01T15:11:04.327Z","creation":"2025-04-06T11:39:18.033Z"},"accession":"S-EPMC11906352","cross_references":{"pubmed":["40033056"],"doi":["10.1038/s41588-025-02108-2"]}}