biostudies-literatureVan Egeren DNational Cancer Institute, USANCI NIH HHS19055https://www.ebi.ac.uk/biostudies/studies/S-EPMC9646734biostudies-literatureUnknown12(1)Patients with non-small cell lung cancer (NSCLC) who have distant metastases have a poor prognosis. To determine which genomic factors of the primary tumor are associated with metastasis, we analyzed data from 759 patients originally diagnosed with stage I-III NSCLC as part of the AACR Project GENIE Biopharma Collaborative consortium. We found that TP53 mutations were significantly associated with the development of new distant metastases. TP53 mutations were also more prevalent in patients with a history of smoking, suggesting that these patients may be at increased risk for distant metastasis. Our results suggest that additional investigation of the optimal management of patients with early-stage NSCLC harboring TP53 mutations at diagnosis is warranted in light of their higher likelihoodScientific reportsGenomic analysis of early-stage lung cancer reveals a role for TP53 mutations in distant metastasis.PMC9646734P30 CA008748Plagianakos DPillai SWeerasinghe RAguilar SStricker TAbraham JHakgor SFoti MVelculescu VEBiswas RCarvajal RFelicen SSawyers CLMacFarland STabernero JStockley TMazor TMastrogiacomo BAndre FZehir ASanders JVan't Veer LBailey NSilva DMicheel CMCao KMoung CRizvi HZhu YRizvi ADang KLeNoue-Newton MCramer JLDogan SDienstmann RLovly CMcCall SJChow HLepisto EMiller DZhao GYu TBesse BNichols CReardon BRueda OMLaucks VPugh TJVan Allen EYe CMishra SKamel-Reid SCaldas CSweet-Cordero EAGreen MQuinn DRudolph JBernard BYu CVoest EHolt MPanageas KSHunter-Zinck HPhilip JStickle NEspinosa-Mendez CLindeman NMacconaill LSammut SJOvalle ALudovic LMeijer GAGalle JManam MBhuiya MAnagnostou VTen Hoeve JNewcomb AOldfield LBerger MFPeters NDucar MHahn WCWatt SCerami EFiandalo MLi MFreeman CELi XLi YHeath APLavery JAWarner JJones LTittel PCoco JJohnson JLiu LLeNoue-Newton MLBifulco CJanne PNuciforo PLilly JRiely GFabbri DHaigis KBierkens MStrickler JHJohnson BJohnson DHsiao SJNimmervoll BRabadan RMorgan AMLindsay JBell JItaliano AWren AGuan MZhang WIngham MTopaloglu USweeney SDel Rossi Svan den Berg JKundra RAnderson IOnodera CMaris JMPiening BBruce JPKohli KGuo XZhang HShah ECooke SWilson MAhmed LSteinhardt GJin GBaras APostle Ade Bruijn IVanCampen JVirtaenen CSholl LUrtis CGardos SGocke CGusev ACushing ORiely GJPang JGuinney JSonke GWarner JLWelsh MMcCarthy CHutchison SLee SPinilla KScoazec JLadanyi MLee JDuBois RChu CTang MViaplana CVivancos ARubinstein SMTramontano AJagannathan PReynolds SMettu NBMichels SSlagel JUrba WKehl KLKhotskaya YChaugai SDeloger MLongtine JOrechia JYang YJBrahmer Jvan de Velde TWang ALueders ATurski MLu ZGao JOchoa AWang LCatalano PAACR Project GENIE Consortium represented by Shawn SweeneyAcebedo AWang PWen LTran-Dien AHudecek JSabatini PVan Nostrand SCde Graaf JSegal JResnick ALeighl NJaneway KAMonkhorst KMittendorf KSchrag DPankhuri WD'Eletto MBenayed RMartin JEHubbard CShivdasani PSrivastava GAlexander SMancuso FMason JLGold PLoriot YSheridan RMartell HJSolit DWalther ZChakravarty DScharpf RBBeaudoin RJawale ADatto MBDoherty GSchultz NKrishna GVassal GSamsom KGSingaravelan NTao JDand DRollins BRoman LCSiu LSchwartz JQuintanar Alfaro ABrannon ARMichor FPark BHVan Egeren DBrenton JDBedard PLTalevich EGross BArcila MELisman AKadri SKumari PHassett MNguyen ABrown SKung ALfalseGenomic analysis of early-stage lung cancer reveals a role for TP53 mutations in distant metastasis.Patients with non-small cell lung cancer (NSCLC) who have distant metastases have a poor prognosis. To determine which genomic factors of the primary tumor are associated with metastasis, we analyzed data from 759 patients originally diagnosed with stage I-III NSCLC as part of the AACR Project GENIE Biopharma Collaborative consortium. We found that TP53 mutations were significantly associated with the development of new distant metastases. TP53 mutations were also more prevalent in patients with a history of smoking, suggesting that these patients may be at increased risk for distant metastasis. Our results suggest that additional investigation of the optimal management of patients with early-stage NSCLC harboring TP53 mutations at diagnosis is warranted in light of their higher likelihood2022-01-01T00:00:00Z2022 Nov2025-04-19T10:37:12.206Z2025-04-19T10:37:12.206ZS-EPMC96467343635196410.1038/s41598-022-21448-1