biostudies-literatureBailey CCancer Research UKNCI NIH HHSNIGMS NIH HHS193-200https://www.ebi.ac.uk/biostudies/studies/S-EPMC11540846biostudies-literatureUnknown635(8037)Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer^1,2. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.1% of tumour samples contain ecDNA. We reveal a pattern highly indicative of tissue-context-based selection for ecDNAs, linking their genomic content to their tissue of origin. We show that not only is ecDNA a mechanism for amplification of driver oncogenes, but it also a mechanism that frequently amplifies immunomodulatory and inflammatory genes, such as those that modulate lymphocyte-mediated immunity and immune effNatureOrigins and impact of extrachromosomal DNA.PMC11540846U24 CA264379OT2 CA278635R01 GM114362CGCATF-2021/100012R01 CA238249Litovchenko MBailey CStavrou GSavage KTaylor Tavares ALBevers RChan GCWilliams EPullinger JLopez FJPich OMcGranahan NGriffin JNThol KMaleady-Crowe FCornish AJFlanagan AMLahnstein LHubbard TJPSharma NBafna VWelland MJMinneci FStuckey ASieghart AZarowiecki MRowan AYang SYCKanu NGenomics England ConsortiumCaulfield MJHamblin AJamal-Hanjani MMueller MLakey AO'Donovan PLuebeck JDameracharla BAmbrose JCScott RHTucci AHung KLHoulston RSBentham RMoutsianas LSwanton CBleda MLeigh SEAPatch CThomas ERABrittain HJones LJArumugam PKasperaviciute DHenderson SPereira MBRogers TBoardman-Pretty FLu WTMoore DAMischel PSMcEntagart MKayikci MThompson SRMurugaesu NLeong IUSWatkins TBKKousathanas AWitkowska KHowitt BEMitchell JTanguy MBrown MAKittel JSmith SCChang HYJackson RGiess ARendon ASosinsky APerez-Gil DNeed ACSawant KNik-Zainal SBoustred CRWeiser NESiddiq ASalgado ROdhams CARahim TWood SMfalseOrigins and impact of extrachromosomal DNA.Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer^1,2. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.1% of tumour samples contain ecDNA. We reveal a pattern highly indicative of tissue-context-based selection for ecDNAs, linking their genomic content to their tissue of origin. We show that not only is ecDNA a mechanism for amplification of driver oncogenes, but it also a mechanism that frequently amplifies immunomodulatory and inflammatory genes, such as those that modulate lymphocyte-mediated immunity and immune eff2024-01-01T00:00:00Z2024 Nov2026-06-01T15:13:55.351Z2025-04-06T10:13:35.089ZS-EPMC115408463950615010.1038/s41586-024-08107-3