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 heterogeneity
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 cells
2021
Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition
Litchfield K, Reading J, Puttick C, Thakkar K, Abbosh C, Bentham R, Watkins T, Rosenthal R, Biswas D, Rowan A, Lim E, Al Bakir M, Turati V, Guerra-Assunção J, Conde L, Furness A, Saini S, Hadrup S, Herrero J, Lee S, Van Loo P, Enver T, Larkin J, Hellmann M, Turajlic S, Quezada S, McGranahan N, Swanton C. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell 2021, 184: 596-614.e14. PMID: 33508232, PMCID: PMC7933824, DOI: 10.1016/j.cell.2021.01.002.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCD8 AntigensChemokine CXCL13Chromosomes, Human, Pair 9Cohort StudiesCyclin D1DNA Copy Number VariationsExomeGene AmplificationHumansImmune Checkpoint InhibitorsImmune EvasionMultivariate AnalysisMutationNeoplasmsPolymorphism, Single NucleotideReceptors, CCR5T-LymphocytesTumor BurdenConceptsTumor mutational burdenTumor-infiltrating lymphocytesHistocompatibility leukocyte antigenCheckpoint inhibitorsCD8 tumor-infiltrating lymphocytesCPI-treated patientsTumor cell-intrinsicClinical outcome criteriaCopy-number analysisCXCL9 expressionCCND1 amplificationMutational burdenLeukocyte antigenTumor typesMultivariate predictorsSingle-cell RNA sequencingAdaptive immunityAssociated with resistanceWhole exomeMicroenvironmental featuresOutcome criteriaCopy-numberFunctional evidenceRNA-seqTumor
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
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