Featured Publications
Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma
Biswas D, Liu Y, Herrero J, Wu Y, Moore D, Karasaki T, Grigoriadis K, Lu W, Veeriah S, Naceur-Lombardelli C, Magno N, Ward S, Frankell A, Hill M, Colliver E, de Carné Trécesson S, East P, Malhi A, Snell D, O’Neill O, Leonce D, Mattsson J, Lindberg A, Micke P, Moldvay J, Megyesfalvi Z, Dome B, Fillinger J, Nicod J, Downward J, Szallasi Z, Hackshaw A, Jamal-Hanjani M, Kanu N, Birkbak N, Swanton C. Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma. Nature Cancer 2025, 6: 86-101. PMID: 39789179, PMCID: PMC11779643, DOI: 10.1038/s43018-024-00883-1.Peer-Reviewed Original ResearchConceptsLung adenocarcinomaStage I diseaseClinicopathological risk factorsSurvival of patientsResponse to treatmentRNA sequencing dataI diseaseSequence dataMetastatic clonesNeedle biopsyIndividual tumorsLung expressionTranscription signalsPrognostic informationWhole exomeExpressed genesChemotherapy sensitivityProspective validationSurvival associationsTranscriptomic heterogeneityHuman tumorsEvolutionary measuresChromosomal instabilityRisk factorsNatural history
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
2020
Pervasive chromosomal instability and karyotype order in tumour evolution
Watkins T, Lim E, Petkovic M, Elizalde S, Birkbak N, Wilson G, Moore D, Grönroos E, Rowan A, Dewhurst S, Demeulemeester J, Dentro S, Horswell S, Au L, Haase K, Escudero M, Rosenthal R, Bakir M, Xu H, Litchfield K, Lu W, Mourikis T, Dietzen M, Spain L, Cresswell G, Biswas D, Lamy P, Nordentoft I, Harbst K, Castro-Giner F, Yates L, Caramia F, Jaulin F, Vicier C, Tomlinson I, Brastianos P, Cho R, Bastian B, Dyrskjøt L, Jönsson G, Savas P, Loi S, Campbell P, Andre F, Luscombe N, Steeghs N, Tjan-Heijnen V, Szallasi Z, Turajlic S, Jamal-Hanjani M, Van Loo P, Bakhoum S, Schwarz R, McGranahan N, Swanton C. Pervasive chromosomal instability and karyotype order in tumour evolution. Nature 2020, 587: 126-132. PMID: 32879494, PMCID: PMC7611706, DOI: 10.1038/s41586-020-2698-6.Peer-Reviewed Original ResearchConceptsSomatic copy number alterationsWhole-genome doublingChromosomal instabilityHuman leukocyte antigenChromosomal instability resultsSomatic copy number alteration analysisLoss of chromosome 8pFocal somatic copy number alterationsLoss of heterozygosityCopy number alterationsMetastatic samplesTumor evolutionKaryotype remodelingChromosome 8q24.1Clear cell renal cellChromosome 1q21Evolutionary eventsHER2+ breast cancerChromosome 8pChromosome 11q13.3Focal amplificationHaploid copiesRecurrent lossSubclonal frequenciesClonal events
2019
5O Using single cell data to validate the cellular origins of a clonal expression biomarker in lung cancer
Biswas D, Birkbak N, McGranahan N, Swanton C. 5O Using single cell data to validate the cellular origins of a clonal expression biomarker in lung cancer. Annals Of Oncology 2019, 30: vii2. DOI: 10.1093/annonc/mdz413.010.Peer-Reviewed Original ResearchNon-small cell lung cancerBreast Cancer Research FoundationTumor sampling biasUniversity College London HospitalGene expression signaturesLung cancerChromosomal instabilityPrognostic gene expression signaturesCancer typesExpression signaturesProstate Cancer FoundationClinicopathological risk factorsCell lung cancerCopy-number gainsAssociated with survivalNIHR BRCIntra-tumor heterogeneityPredictive of outcomeExperimental Cancer Medicine CentreLondon HospitalLung Cancer CentreCancer Research UKCancer cell proliferationSingle-cell dataRNA sequencing data
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