Featured Publications
A clonal expression biomarker associates with lung cancer mortality
Biswas D, Birkbak N, Rosenthal R, Hiley C, Lim E, Papp K, Boeing S, Krzystanek M, Djureinovic D, La Fleur L, Greco M, Döme B, Fillinger J, Brunnström H, Wu Y, Moore D, Skrzypski M, Abbosh C, Litchfield K, Al Bakir M, Watkins T, Veeriah S, Wilson G, Jamal-Hanjani M, Moldvay J, Botling J, Chinnaiyan A, Micke P, Hackshaw A, Bartek J, Csabai I, Szallasi Z, Herrero J, McGranahan N, Swanton C. A clonal expression biomarker associates with lung cancer mortality. Nature Medicine 2019, 25: 1540-1548. PMID: 31591602, PMCID: PMC6984959, DOI: 10.1038/s41591-019-0595-z.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerClinicopathological risk factorsCell lung cancerLung cancer mortalityPrognostic gene expression signaturesCancer cell proliferationGene expression signaturesCancer mortalityLung cancerRisk factorsExpression-based biomarkersCopy number gainsDisease subtypesClinical descriptorsTranscriptomic biomarkersIndividual tumorsCancer typesDiagnostic precisionMolecular biomarkersExpression signaturesCell proliferationDNA copy number gainsBiomarkersPatientsIntratumor heterogeneityA local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer
Wu Y, Biswas D, Usaite I, Angelova M, Boeing S, Karasaki T, Veeriah S, Czyzewska-Khan J, Morton C, Joseph M, Hessey S, Reading J, Georgiou A, Al-Bakir M, McGranahan N, Jamal-Hanjani M, Hackshaw A, Quezada S, Hayday A, Swanton C. A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer. Nature Cancer 2022, 3: 696-709. PMID: 35637401, PMCID: PMC9236901, DOI: 10.1038/s43018-022-00376-z.Peer-Reviewed Original ResearchConceptsT cell populationsT cellsLung tissueLung cancerCD8+ T cellsNonsmall-cell lung cancerNonsmall cell lung cancerEffector memory phenotypeT cell compartmentCell lung cancerAssociated with survivalNonmalignant lung tissuesStem-like featuresNontumor lung tissuesT cell biologyHuman lung tissueImmunotherapeutic strategiesMemory phenotypeNatural killerLung tumorsTissue-residentPost-surgeryResident memoryMurine tissuesTumor
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, Martínez-Ruiz C, Bakir M, Pich O, Watkins T, Lim E, Huebner A, Moore D, Godin-Heymann N, L’Hernault A, Bye H, Odell A, Roberts 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 cellsEvolutionary characterization of lung adenocarcinoma morphology in TRACERx
Karasaki T, Moore D, Veeriah S, Naceur-Lombardelli C, Toncheva A, Magno N, Ward S, Bakir M, Watkins T, Grigoriadis K, Huebner A, Hill M, Frankell A, Abbosh C, Puttick C, Zhai H, Gimeno-Valiente F, Saghafinia S, Kanu N, Dietzen M, Pich O, Lim E, Martínez-Ruiz C, Black J, Biswas D, Campbell B, Lee C, Colliver E, Enfield K, Hessey S, Hiley C, Zaccaria S, Litchfield K, Birkbak N, Cadieux E, Demeulemeester J, Van Loo P, Adusumilli P, Tan K, Cheema W, Sanchez-Vega F, Jones D, Rekhtman N, Travis W, Hackshaw A, Marafioti T, Salgado R, Le Quesne J, Nicholson A, McGranahan N, Swanton C, Jamal-Hanjani M. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx. Nature Medicine 2023, 29: 833-845. PMID: 37045996, PMCID: PMC7614478, DOI: 10.1038/s41591-023-02230-w.Peer-Reviewed Original ResearchConceptsPrimary tumor regionLung adenocarcinomaPresence of micropapillary patternLoss of chromosome 3pSolid pattern tumorsHigh-grade patternsClonal evolution analysisSomatic copy number alterationsTumor regionLoss of heterozygosityWhole-exome sequencing dataCopy number alterationsAdenocarcinoma morphologyIntrathoracic recurrenceLepidic tumorsRNA sequencing dataMicropapillary patternRelapse riskGene alterationsMetastatic samplesHistological spectrumMicropapillary tumorsChromosome 3pHigh-gradeHistopathological analysisThe 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, Martínez-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
2022
RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma
East P, Kelly G, Biswas D, Marani M, Hancock D, Creasy T, Sachsenmeier K, Swanton C, Downward J, de Carné Trécesson S. RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma. Nature Communications 2022, 13: 5632. PMID: 36163168, PMCID: PMC9512813, DOI: 10.1038/s41467-022-33290-0.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungGenes, rasHumansLung NeoplasmsMutationProto-Oncogene Proteins p21(ras)Ras ProteinsConceptsResponse to chemotherapyLung adenocarcinomaRas oncogene activationOncogenic activityKRAS wild-type tumorsReduced response to chemotherapyWild-type tumorsKRAS mutant tumorsResistance to therapyCohort of patientsAdverse clinical outcomesResponse to treatmentRAS pathway activationActive patient groupAggressive diseaseMutant tumorsKRAS mutationsClinical outcomesPreclinical studiesActivating mutationsClinical decision-makingGenetic alterationsPatient stratificationPatient groupKRAS
2020
The T cell differentiation landscape is shaped by tumour mutations in lung cancer
Ghorani E, Reading J, Henry J, Massy M, Rosenthal R, Turati V, Joshi K, Furness A, Ben Aissa A, Saini S, Ramskov S, Georgiou A, Sunderland M, Wong Y, Mucha M, Day W, Galvez-Cancino F, Becker P, Uddin I, Oakes T, Ismail M, Ronel T, Woolston A, Jamal-Hanjani M, Veeriah S, Birkbak N, Wilson G, Litchfield K, Conde L, Guerra-Assunção J, Blighe K, Biswas D, Salgado R, Lund T, Bakir M, Moore D, Hiley C, Loi S, Sun Y, Yuan Y, AbdulJabbar K, Turajilic S, Herrero J, Enver T, Hadrup S, Hackshaw A, Peggs K, McGranahan N, Chain B, Swanton C, Quezada S. The T cell differentiation landscape is shaped by tumour mutations in lung cancer. Nature Cancer 2020, 1: 546-561. PMID: 32803172, PMCID: PMC7115931, DOI: 10.1038/s43018-020-0066-y.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell DifferentiationHumansLung NeoplasmsMutationConceptsNon-small cell lung cancerTumor mutational burdenT cellsUntreated non-small cell lung cancerLung cancerCD8 T cell differentiationHigh-dimensional flow cytometryAssociated with poor survivalPersistent antigen exposureCD8 T cellsCD4 T cellsCell lung cancerT cell functionT cell differentiationImmunotherapy outcomesTumor neoantigensUntreated tumorsMutational burdenAntigen exposureTumor mutationsPoor survivalCancer cohortGene signatureTherapeutic manipulationFlow cytometry