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
The evolution of lung cancer and impact of subclonal selection in TRACERx
Frankell A, Dietzen M, Al Bakir M, Lim E, Karasaki T, Ward S, Veeriah S, Colliver E, Huebner A, Bunkum A, Hill M, Grigoriadis K, Moore D, Black J, Liu W, Thol K, Pich O, Watkins T, Naceur-Lombardelli C, Cook D, Salgado R, Wilson G, Bailey C, Angelova M, Bentham R, MartÃnez-Ruiz C, Abbosh C, Nicholson A, Le Quesne J, Biswas D, Rosenthal R, Puttick C, Hessey S, Lee C, Prymas P, Toncheva A, Smith J, Xing W, Nicod J, Price G, Kerr K, Naidu B, Middleton G, Blyth K, Fennell D, Forster M, Lee S, Falzon M, Hewish M, Shackcloth M, Lim E, Benafif S, Russell P, Boleti E, Krebs M, Lester J, Papadatos-Pastos D, Ahmad T, Thakrar R, Lawrence D, Navani N, Janes S, Dive C, Blackhall F, Summers Y, Cave J, Marafioti T, Herrero J, Quezada S, Peggs K, Schwarz R, Van Loo P, Miedema D, Birkbak N, Hiley C, Hackshaw A, Zaccaria S, Jamal-Hanjani M, McGranahan N, Swanton C. The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature 2023, 616: 525-533. PMID: 37046096, PMCID: PMC10115649, DOI: 10.1038/s41586-023-05783-5.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerDisease-free survivalCell lung cancerWhole-genome doublingLung cancerLung adenocarcinomaAssociated with shorter disease-free survivalShorter disease-free survivalEvolution of lung cancerPattern of relapseSubclonal selectionPrimary study endpointHistory of smokingSubclonal expansionsCopy number instabilityEGFR mutationsCancer-associated mortalityCopy number heterogeneityClinical outcomesStudy endpointIntratumour heterogeneityNever-smokersClonal expansionFollow-upOncogenic isoform
2021
Impact of cancer evolution on immune surveillance and checkpoint inhibitor response
Wu Y, Biswas D, Swanton C. Impact of cancer evolution on immune surveillance and checkpoint inhibitor response. Seminars In Cancer Biology 2021, 84: 89-102. PMID: 33631295, PMCID: PMC9253787, DOI: 10.1016/j.semcancer.2021.02.013.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsCheckpoint inhibitor therapyCheckpoint inhibitorsIntratumour heterogeneityImmune surveillancePatient's response to immune checkpoint inhibitorsResponse to immune checkpoint inhibitorsCheckpoint inhibitor responseProportion of patientsStandard of carePredictive biomarkersStratify patientsImmune evasionDiagnostic accuracyInhibitor responseImmune systemMechanisms of genetic instabilityPatientsGenetic instabilityCancer evolutionTherapyCancerSurveillanceInhibitorsIntratumour
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