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 tumorsThe 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
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