2023
Evolutionary 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 ResearchConceptsResponse 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