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
Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA
Abbosh C, Frankell A, Harrison T, Kisistok J, Garnett A, Johnson L, Veeriah S, Moreau M, Chesh A, Chaunzwa T, Weiss J, Schroeder M, Ward S, Grigoriadis K, Shahpurwalla A, Litchfield K, Puttick C, Biswas D, Karasaki T, Black J, MartÃnez-Ruiz C, Bakir M, Pich O, Watkins T, Lim E, Huebner A, Moore D, Godin-Heymann N, L’Hernault A, Bye H, Odell A, Kalavakur P, Gomes F, Patel A, Manzano E, Hiley C, Carey N, Riley J, Cook D, Hodgson D, Stetson D, Barrett J, Kortlever R, Evan G, Hackshaw A, Daber R, Shaw J, Aerts H, Licon A, Stahl J, Jamal-Hanjani M, Birkbak N, McGranahan N, Swanton C. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA. Nature 2023, 616: 553-562. PMID: 37055640, PMCID: PMC7614605, DOI: 10.1038/s41586-023-05776-4.Peer-Reviewed Original ResearchConceptsCirculating tumor DNANon-small-cell lung cancerMetastatic disseminationClinical outcomesPlasma samplesEarly-stage non-small-cell lung cancerCirculating tumor DNA levelsCirculating tumor DNA detectionCytotoxic adjuvant therapyPreoperative ctDNA detectionResidual tumor cellsLongitudinal plasma samplesCancer cell fractionBiomarker of relapseProcess of metastatic disseminationAnalysis of plasma samplesClinical relapseDisease relapseAdjuvant therapyTumor DNAPreoperative plasmaRadiological surveillanceCtDNA detectionPatient cohortTumor cells
2019
Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse
Chemi F, Rothwell D, McGranahan N, Gulati S, Abbosh C, Pearce S, Zhou C, Wilson G, Jamal-Hanjani M, Birkbak N, Pierce J, Kim C, Ferdous S, Burt D, Slane-Tan D, Gomes F, Moore D, Shah R, Al Bakir M, Hiley C, Veeriah S, Summers Y, Crosbie P, Ward S, Mesquita B, Dynowski M, Biswas D, Tugwood J, Blackhall F, Miller C, Hackshaw A, Brady G, Swanton C, Dive C. Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse. Nature Medicine 2019, 25: 1534-1539. PMID: 31591595, PMCID: PMC6986897, DOI: 10.1038/s41591-019-0593-1.Peer-Reviewed Original ResearchConceptsNon-small-cell lung cancerEarly-stage non-small-cell lung cancerDisease relapseGenomic profilingHigh risk of recurrenceDetection of circulating tumor cellsRisk of recurrenceTumor cell disseminationTime of surgeryPredictors of relapsePotential clinical utilityCurative intentPrimary tumorSurgical resectionTumor resectionTumor stagePredicting relapseCell disseminationTumor cellsLung cancerMutational overlapRelapseMultivariate analysisSurgeryHigh risk
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