SkiptomaincontentThankyouforvisitingnature.com.YouareusingabrowserversionwithlimitedsupportforCSS.Toobtainthebestexperience,werecommendyouuseamoreuptodatebrowser(orturnoffcompatibilitymodeinInternetExplorer).Inthemeantime,toensurecontinuedsupport,wearedisplayingthesitewithoutstylesandJavaScript.AdvertisementnaturenaturecommunicationsarticlesarticleThegenomiclandscapeofEpstein-Barrvirus-associatedpulmonarylymphoepithelioma-likecarcinomaDownloadPDFSubjectsCancergenomicsLungcancerAbstractPulmonarylymphoepithelioma-likecarcinoma(LELC)isarareanddistinctsubtypeofprimarylungcancercharacterizedbyEpstein-Barrvirus(EBV)infection.Herein,wereportedthemutationallandscapeofpulmonaryLELCusingwhole-exomesequencing,targeteddeepsequencingandsingle-nucleotidepolymorphismarrays.Weidentifyalowdegreeofsomaticmutationbutwidespreadexistenceofcopynumbervariations.Werevealpredominantsignature2mutationsandfrequentlossoftypeIinterferongenesthatareinvolvedinthehost-viruscounteraction.Integratedanalysisshowsenrichmentofgeneticlesionsaffectingseveralcriticalpathways,includingNF-κB,JAK/STAT,andcellcycle.Notably,multi-dimensionalcomparisonunveilsthatpulmonaryLELCresembleNPCbutareclearlydifferentfromotherlungcancers,naturalkiller/T-celllymphomaorEBV-relatedgastriccancerintermsofgeneticfeatures.Inall,ourstudyillustratesadistinctgenomiclandscapeofpulmonaryLELCandprovidesaroadmaptofacilitategenome-guidedpersonalizedtreatment.DownloadPDFIntroductionPulmonarylymphoepithelioma-likecarcinoma(LELC)isararesubtypeofprimarylungcancerthathistologicallyresemblesundifferentiatednasopharyngealcarcinoma(NPC)1.Firstreportedin1987,pulmonaryLELChasbeenrecognizedtobecloselyrelatedtoEpstein–Barrvirus(EBV)infection2,3.Inthe2015WorldHealthOrganization(WHO)ClassificationofLungTumors,pulmonaryLELCwasmovedfromlargecellcarcinomatootherandunclassifiedcarcinomas4.Comparedwithothertypesoflungcancers,pulmonaryLELChasdistinctclinicopathologicalfeatures.ItpreferentiallyaffectsAsiannon-smokersofyoungerageandhasintensivetumorinfiltra