2024
TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling
Lu W, Zalmas L, Bailey C, Black J, Martinez-Ruiz C, Pich O, Gimeno-Valiente F, Usaite I, Magness A, Thol K, Webber T, Jiang M, Saunders R, Liu Y, Biswas D, Ige E, Aerne B, Grönroos E, Venkatesan S, Stavrou G, Karasaki T, Al Bakir M, Renshaw M, Xu H, Schneider-Luftman D, Sharma N, Tovini L, Jamal-Hanjani M, McClelland S, Litchfield K, Birkbak N, Howell M, Tapon N, Fugger K, McGranahan N, Bartek J, Kanu N, Swanton C. TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling. Nature Cell Biology 2024, 27: 154-168. PMID: 39738653, PMCID: PMC11735399, DOI: 10.1038/s41556-024-01558-w.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCadherinsCarcinoma, Non-Small-Cell LungCell Line, TumorChromosomal InstabilityGene Expression Regulation, NeoplasticHippo Signaling PathwayHumansLung NeoplasmsMiceMitosisProtein Serine-Threonine KinasesSignal TransductionTranscription FactorsYAP-Signaling ProteinsConceptsWhole-genome doublingStructural chromosome instabilityChromosomal instabilityHomologous recombinationNumerical chromosome instabilityNon-small-cell lung cancerHR deficiencyPersistent replication stressGenome doublingRadial chromosomesHippo signalingReplication stressChromosomal translocationsEvolutionary adaptationDriver eventsGenetic alterationsFAT1Increased tumor heterogeneityChromosomeCO depletionYAP1Downstream mechanismsRepair deficiencyIntratumour heterogeneityExperimental approach
2023
Abstract LB237: Functional characterisation of TRACERx reveals mechanisms of NSCLC evolution
Lu W, Zalmas L, Bailey C, Pich O, Ruiz C, Black J, Stavrou G, Biswas D, Gimeno-Valiente F, Litchfield K, Bartek J, McGranahan N, Kanu N, Swanton C. Abstract LB237: Functional characterisation of TRACERx reveals mechanisms of NSCLC evolution. Cancer Research 2023, 83: lb237-lb237. DOI: 10.1158/1538-7445.am2023-lb237.Peer-Reviewed Original ResearchNon-small cell lung cancerElevated chromosomal instabilityWhole-genome doublingChromosomal instabilityIntratumoral heterogeneityHomologous recombination repairDNA damage responseAmerican Association for Cancer Research annual meetingsPC9 cellsRates of acquired resistanceIncreased intratumoral heterogeneityCell lung cancerIncreased CINDrug-resistant tumorsGenome doublingFunctional characterisationStructural chromosome instabilityWhole-genome doubling eventsFAT1 mutationsHomologous recombination repair pathwayBRCA1 foci formationChromosomal gainsMitotic error rateTargeted therapySolid tumors
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