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Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012 Mar 8;366(10):883–892.GerlingerMRowanAJHorswellSMathMLarkinJEndesfelderDIntratumor heterogeneity and branched evolution revealed by multiregion sequencing2012Mar836610883892Search in Google Scholar
Saunders NA, Simpson F, Thompson EW, Hill MM, Endo-Munoz L, Leggatt G, Minchin RF, Guminski A. Role of intratumoural heterogeneity in cancer drug resistance: molecular and clinical perspectives. EMBO Mol Med. 2012 Aug;4(8):675–84.SaundersNASimpsonFThompsonEWHillMMEndo-MunozLLeggattGMinchinRFGuminskiARole of intratumoural heterogeneity in cancer drug resistance: molecular and clinical perspectives2012Aug4867584Search in Google Scholar
Caswell DR, Swanton C. The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome. BMC Med. 2017 Jul 18;15(1):133.CaswellDRSwantonCThe role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome2017Jul18151133Search in Google Scholar
Venkatesan S, Swanton C. Tumor Evolutionary Principles: How Intratumor Heterogeneity Influences Cancer Treatment and Outcome. Am Soc Clin Oncol Educ Book. 2016;35:e141–9.VenkatesanSSwantonCTumor Evolutionary Principles: How Intratumor Heterogeneity Influences Cancer Treatment and Outcome201635e1419Search in Google Scholar
Hiley CT, Swanton C. Spatial and temporal cancer evolution: causes and consequences of tumour diversity. Clin Med (Lond). 2014 Dec;14 Suppl 6:s33–7.HileyCTSwantonCSpatial and temporal cancer evolution: causes and consequences of tumour diversity2014Dec14Suppl 6s337Search in Google Scholar
Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 2018 Feb;15(2):81–94.Dagogo-JackIShawATTumour heterogeneity and resistance to cancer therapies2018Feb1528194Search in Google Scholar
McGranahan N, Swanton C. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell. 2015 Jan 12;27(1):15–26.McGranahanNSwantonCBiological and therapeutic impact of intratumor heterogeneity in cancer evolution2015Jan122711526Search in Google Scholar
McGranahan N, Swanton C. Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future. Cell. 2017 Feb 9;168(4):613–628.McGranahanNSwantonCClonal Heterogeneity and Tumor Evolution: Past, Present, and the Future2017Feb91684613628Search in Google Scholar
Kuipers J, Jahn K, Beerenwinkel N. Advances in understanding tumour evolution through single-cell sequencing. Biochim Biophys Acta. 2017 Apr;1867(2):127–138.KuipersJJahnKBeerenwinkelNAdvances in understanding tumour evolution through single-cell sequencing2017Apr18672127138Search in Google Scholar
Navin, N. E. (2014). Cancer genomics: one cell at a time. Genome Biology, 15(8), 452.NavinN. E.2014Cancer genomics: one cell at a time158452Search in Google Scholar
Wang Y, Waters J, Leung ML, Unruh A, Roh W, Shi X, et al. Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature. 2014;512(7513):155–160.WangYWatersJLeungMLUnruhARohWShiXClonal evolution in breast cancer revealed by single nucleus genome sequencing20145127513155160Search in Google Scholar
Francis JM, Zhang CZ, Maire CL, Jung J, Manzo VE, Adalsteinsson VA, Homer H, Haidar S, Blumenstiel B, Pedamallu CS, Ligon AH, Love JC, Meyerson M, Ligon KL. EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov. 2014 Aug;4(8):956–71.FrancisJMZhangCZMaireCLJungJManzoVEAdalsteinssonVAHomerHHaidarSBlumenstielBPedamalluCSLigonAHLoveJCMeyersonMLigonKLEGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing2014Aug4895671Search in Google Scholar
Navin, N., Kendall, J., Troge, J., Andrews, P., Rodgers, L., McIndoo, J., … Wigler, M. (2011). Tumor Evolution Inferred by Single Cell Sequencing. Nature, 472(7341), 90–94.NavinN.KendallJ.TrogeJ.AndrewsP.RodgersL.McIndooJ.WiglerM.2011Tumor Evolution Inferred by Single Cell Sequencing47273419094Search in Google Scholar
Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, et al, TRACERx Consortium. Tracking the Evolution of Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Jun 1;376(22):2109–2121Jamal-HanjaniMWilsonGAMcGranahanNBirkbakNJWatkinsTBKVeeriahSTRACERx ConsortiumTracking the Evolution of Non-Small-Cell Lung Cancer2017Jun1376222109212Search in Google Scholar
Shibata T. Current and future molecular profiling of cancer by next-generation sequencing. Jpn J Clin Oncol. 2015 Oct;45(10):895–9.ShibataTCurrent and future molecular profiling of cancer by next-generation sequencing2015Oct45108959Search in Google Scholar
Mar N, Vredenburgh JJ, Wasser JS. Targeting HER2 in the treatment of non-small cell lung cancer. Lung Cancer. 2015 Mar;87(3):220–5.MarNVredenburghJJWasserJSTargeting HER2 in the treatment of non-small cell lung cancer2015Mar8732205Search in Google Scholar
Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511:543–50.Cancer Genome Atlas Research NetworkComprehensive molecular profiling of lung adenocarcinoma201451154350Search in Google Scholar
Gerlinger M, Swanton C. How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine. Br J Cancer. 2010 Oct 12;103(8):1139–43.GerlingerMSwantonCHow Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine2010Oct121038113943Search in Google Scholar
Neelakantan, D. et al. (2015) Intratumoral heterogeneity: Clonal cooperation in epithelial-to-mesenchymal transition and metastasis. Cell Adh Migr, 9, 265–76.NeelakantanD.2015Intratumoral heterogeneity: Clonal cooperation in epithelial-to-mesenchymal transition and metastasis926576Search in Google Scholar
Saber A, Hiltermann TJN, Kok K, Terpstra MM, de Lange K, Timens W, Groen HJM, van den Berg A. Mutation patterns in small cell and non-small cell lung cancer patients suggest a different level of heterogeneity between primary and metastatic tumors. Carcinogenesis. 2017 Feb 1;38(2):144–151.SaberAHiltermannTJNKokKTerpstraMMde LangeKTimensWGroenHJMvan den BergAMutation patterns in small cell and non-small cell lung cancer patients suggest a different level of heterogeneity between primary and metastatic tumors2017Feb1382144151Search in Google Scholar
Kalikaki A, Koutsopoulos A, Trypaki M, Souglakos J, Stathopoulos E, Georgoulias V, Mavroudis D, Voutsina A (2008) Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC. Br J. Cancer 99(6):923–929.KalikakiAKoutsopoulosATrypakiMSouglakosJStathopoulosEGeorgouliasVMavroudisDVoutsinaA2008Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC996923929Search in Google Scholar
de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC, Yates L, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science. 2014 Oct 10;346(6206):251–6.de BruinECMcGranahanNMitterRSalmMWedgeDCYatesLSpatial and temporal diversity in genomic instability processes defines lung cancer evolution2014Oct1034662062516Search in Google Scholar
Izumchenko E, Chang X, Brait M, Fertig E, Kagohara LT, Bedi A, Marchionni L, Agrawal N, Ravi R, Jones S, Hoque MO, Westra WH, Sidransky D. Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA. Nat Commun. 2015 Sep 16;6:8258.IzumchenkoEChangXBraitMFertigEKagoharaLTBediAMarchionniLAgrawalNRaviRJonesSHoqueMOWestraWHSidranskyDTargeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA2015Sep1668258Search in Google Scholar
Sherwood J, Dearden S, Ratcliffe M, Walker J. Mutation status concordance between primary lesions and metastatic sites of advanced non-small-cell lung cancer and the impact of mutation testing methodologies: a literature review. J Exp Clin Cancer Res. 2015 Sep 4;34:92.SherwoodJDeardenSRatcliffeMWalkerJMutation status concordance between primary lesions and metastatic sites of advanced non-small-cell lung cancer and the impact of mutation testing methodologies: a literature review2015Sep43492Search in Google Scholar
Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep (2012) 14(1):48–54.NayakLLeeEQWenPYEpidemiology of brain metastases20121414854Search in Google Scholar
Park S, Holmes-Tisch AJ, Cho EY, Shim YM, Kim J, Kim HS, et al. Discordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer. J Thorac Oncol. 2009;4:809–15.ParkSHolmes-TischAJChoEYShimYMKimJKimHSDiscordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer2009480915Search in Google Scholar
Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, et al. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discov. 2015 Nov;5(11):1164–1177.BrastianosPKCarterSLSantagataSCahillDPTaylor-WeinerAJonesRTGenomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets2015Nov51111641177Search in Google Scholar
Izumchenko E, Chang X, Brait M, Fertig E, Kagohara LT, Bedi A, et al. Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA. Nat Commun. 2015 Sep 16;6:8258.IzumchenkoEChangXBraitMFertigEKagoharaLTBediATargeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA2015Sep1668258Search in Google Scholar
Hata AN, Niederst MJ, Archibald HL, Gomez-Caraballo M, Siddiqui FM, Mulvey HE, et al. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nat Med. 2016 Mar;22(3):262–9.HataANNiederstMJArchibaldHLGomez-CaraballoMSiddiquiFMMulveyHETumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition2016Mar2232629Search in Google Scholar
Piotrowska Z, Niederst MJ, Karlovich CA, Wakelee HA, Neal JW, Mino-Kenudson M, et al. Heterogeneity Underlies the Emergence of EGFRT790 Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third-Generation EGFR Inhibitor. Cancer Discov. 2015 Jul;5(7):713–22.PiotrowskaZNiederstMJKarlovichCAWakeleeHANealJWMino-KenudsonMHeterogeneity Underlies the Emergence of EGFRT790 Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third-Generation EGFR Inhibitor2015Jul5771322Search in Google Scholar
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Engelman, J. A. (2011). Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors. Science Translational Medicine, 3(75), 75ra26.SequistL. V.WaltmanB. A.Dias-SantagataD.DigumarthyS.TurkeA. B.FidiasP.EngelmanJ. A.2011Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors37575ra26Search in Google Scholar
Song A, Kim TM, Kim DW, Kim S, Keam B, Lee SH, Heo DS. Molecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer. Clin Cancer Res. 2015 May 15;21(10):2379–87.SongAKimTMKimDWKimSKeamBLeeSHHeoDSMolecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer2015May152110237987Search in Google Scholar
Drilon A, Somwar R, Wagner JP, Vellore NA, Eide CA, Zabriskie MS, et al. A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-Rearranged Lung Cancer. Clin Cancer Res. 2016 May 15;22(10):2351–8.DrilonASomwarRWagnerJPVelloreNAEideCAZabriskieMSA Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-Rearranged Lung Cancer2016May15221023518Search in Google Scholar
Awad MM, Katayama R, McTigue M, Liu W, Deng YL, Brooun A, et al. Acquired resistance to crizotinib from a mutation in CD74-ROS1. N Engl J Med. 2013 Jun 20;368(25):2395–401.AwadMMKatayamaRMcTigueMLiuWDengYLBroounAAcquired resistance to crizotinib from a mutation in CD74-ROS12013Jun20368252395401Search in Google Scholar
Gerlinger M, Norton L, Swanton C. Acquired resistance to crizotinib from a mutation in CD74-ROS1. N Engl J Med. 2013 Sep 19;369(12):1172–3.GerlingerMNortonLSwantonCAcquired resistance to crizotinib from a mutation in CD74-ROS12013Sep193691211723Search in Google Scholar
Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017 Apr 26;545(7655):446–451.AbboshCBirkbakNJWilsonGAJamal-HanjaniMConstantinTSalariRPhylogenetic ctDNA analysis depicts early-stage lung cancer evolution2017Apr265457655446451Search in Google Scholar
Hayes DF, Paoletti C. Circulating tumour cells: insights into tumour heterogeneity. J Intern Med. 2013 Aug;274(2):137–43.HayesDFPaolettiCCirculating tumour cells: insights into tumour heterogeneity2013Aug274213743Search in Google Scholar
Santarpia M, Liguori A, Karachaliou N, Gonzalez-Cao M, Daffinà MG, D’Aveni A, Marabello G, Altavilla G, Rosell R. Osimertinib in the treatment of non-small-cell lung cancer: design, development and place in therapy. Lung Cancer (Auckl). 2017 Aug 18;8:109–125.SantarpiaMLiguoriAKarachaliouNGonzalez-CaoMDaffinàMGD’AveniAMarabelloGAltavillaGRosellROsimertinib in the treatment of non-small-cell lung cancer: design, development and place in therapy2017Aug188109125Search in Google Scholar
Santarpia M, Liguori A, Karachaliou N, Gonzalez-Cao M, Daffinà MG, D’Aveni A, et al. Osimertinib in the treatment of non-small-cell lung cancer: design, development and place in therapy. Lung Cancer (Auckl). 2017 Aug 18;8:109–125.SantarpiaMLiguoriAKarachaliouNGonzalez-CaoMDaffinàMGD’AveniAOsimertinib in the treatment of non-small-cell lung cancer: design, development and place in therapy2017Aug188109125Search in Google Scholar
Navin, N. E. (2015). The first five years of single-cell cancer genomics and beyond. Genome Research, 25(10), 1499–1507.NavinN. E.2015The first five years of single-cell cancer genomics and beyond251014991507Search in Google Scholar
Craigie M, Squires J, Miles K. Can CT measures of tumour heterogeneity stratify risk for nodal metastasis in patients with non-small cell lung cancer? Clin Radiol. 2017 Oct;72(10):899.e1–899.e7CraigieMSquiresJMilesKCan CT measures of tumour heterogeneity stratify risk for nodal metastasis in patients with non-small cell lung cancer?2017Oct7210899.e1899.e7Search in Google Scholar
Nair VS, Gevaert O, Davidzon G, Napel S, Graves EE, Hoang CD, et al. Prognostic PET 18F-FDG uptake imaging features are associated with major oncogenomic alterations in patients with resected non-small cell lung cancer. Cancer research. 2012; 72(15):3725±34.NairVSGevaertODavidzonGNapelSGravesEEHoangCDPrognostic PET 18F-FDG uptake imaging features are associated with major oncogenomic alterations in patients with resected non-small cell lung cancer20127215372534Search in Google Scholar
Park S, Ha S, Lee SH, Paeng JC, Keam B, Kim TM, et al. Intratumoral heterogeneity characterized by pretreatment PET in non-small cell lung cancer patients predicts progression-free survival on EGFR tyrosine kinase inhibitor. PLoS One. 2018 Jan 31;13(1):e0189766.ParkSHaSLeeSHPaengJCKeamBKimTMIntratumoral heterogeneity characterized by pretreatment PET in non-small cell lung cancer patients predicts progression-free survival on EGFR tyrosine kinase inhibitor2018Jan31131e0189766Search in Google Scholar
Dong ZY, Zhai HR, Hou QY, Su J, Liu SY, Yan HH, et al. Mixed Responses to Systemic Therapy Revealed Potential Genetic Heterogeneity and Poor Survival in Patients with Non-Small Cell Lung Cancer. Oncologist. 2017 Jan;22(1):61–69.DongZYZhaiHRHouQYSuJLiuSYYanHHMixed Responses to Systemic Therapy Revealed Potential Genetic Heterogeneity and Poor Survival in Patients with Non-Small Cell Lung Cancer2017Jan2216169Search in Google Scholar
Tricker EM, Xu C, Uddin S, Capelletti M, Ercan D, Ogino A, Pratilas CA, Rosen N, Gray NS, Wong KK, Jänne PA. Combined EGFR/MEK Inhibition Prevents the Emergence of Resistance in EGFR-Mutant Lung Cancer. Cancer Discov. 2015 Sep;5(9):960–971.TrickerEMXuCUddinSCapellettiMErcanDOginoAPratilasCARosenNGrayNSWongKKJännePACombined EGFR/MEK Inhibition Prevents the Emergence of Resistance in EGFR-Mutant Lung Cancer2015Sep59960971Search in Google Scholar
Chaib I, Karachaliou N, Pilotto S, Codony Servat J, Cai X, Li X, et al. Co-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC. J Natl Cancer Inst. 2017 Sep 1;109(9).ChaibIKarachaliouNPilottoSCodony ServatJCaiXLiXCo-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC2017Sep11099Search in Google Scholar
Niederst MJ, Hu H, Mulvey HE, Lockerman EL, Garcia AR, Piotrowska Z, Sequist LV, Engelman JA. The Allelic Context of the C797S Mutation Acquired upon Treatment with Third-Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment Strategies. Clin Cancer Res. 2015 Sep 1;21(17):3924–33.NiederstMJHuHMulveyHELockermanELGarciaARPiotrowskaZSequistLVEngelmanJAThe Allelic Context of the C797S Mutation Acquired upon Treatment with Third-Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment Strategies2015Sep12117392433Search in Google Scholar
Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell. 2012 Sep14;150(6):1121–34.GovindanRDingLGriffithMSubramanianJDeesNDKanchiKLGenomic landscape of non-small cell lung cancer in smokers and never-smokers2012Sep141506112134Search in Google Scholar
Casadevall D, Clavé S, Taus Á, Hardy-Werbin M, Rocha P, Lorenzo M, Menéndez S, Salido M, Albanell J, Pijuan L, Arriola E. Heterogeneity of Tumor and Immune Cell PD-L1 Expression and Lymphocyte Counts in Surgical NSCLC Samples. Clin Lung Cancer. 2017 Nov;18(6):682–691.e5.CasadevallDClavéSTausÁHardy-WerbinMRochaPLorenzoMMenéndezSSalidoMAlbanellJPijuanLArriolaEHeterogeneity of Tumor and Immune Cell PD-L1 Expression and Lymphocyte Counts in Surgical NSCLC Samples2017Nov186682691.e5Search in Google Scholar
Bassanelli M, Sioletic S, Martini M, Giacinti S, Viterbo A, Staddon A, Liberati F, Ceribelli A. Heterogeneity of PD-L1 Expression and Relationship with Biology of NSCLC. Anticancer Res. 2018 Jul;38(7):3789–3796.BassanelliMSioleticSMartiniMGiacintiSViterboAStaddonALiberatiFCeribelliAHeterogeneity of PD-L1 Expression and Relationship with Biology of NSCLC2018Jul38737893796Search in Google Scholar
Lee WC, Diao L, Wang J, Zhang J, Roarty EB, Varghese S, Chow CW, Fujimoto J, Behrens C, Cascone T, Peng W, Kalhor N, Moran CA, Weissferdt A, Johnson FM, William WN Jr, Swisher SG, Lee JJ, Hong WK, Heymach JV, Wistuba II, Futreal PA, Zhang J. Multiregion gene expression profiling reveals heterogeneity in molecular subtypes and immunotherapy response signatures in lung cancer. Mod Pathol. 2018 Jun;31(6):947–955.LeeWCDiaoLWangJZhangJRoartyEBVargheseSChowCWFujimotoJBehrensCCasconeTPengWKalhorNMoranCAWeissferdtAJohnsonFMWilliamWNJrSwisherSGLeeJJHongWKHeymachJVWistubaIIFutrealPAZhangJMultiregion gene expression profiling reveals heterogeneity in molecular subtypes and immunotherapy response signatures in lung cancer2018Jun316947955Search in Google Scholar