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dc.contributor.authorBruin, Elza C de
dc.contributor.authorMcGranahan, Nicholas
dc.contributor.authorMitter, Richard
dc.contributor.authorSalm, Max
dc.contributor.authorWedge, David C
dc.contributor.authorYates, Lucy
dc.contributor.authorJamal-Hanjani, Mariam
dc.contributor.authorHorswell, Stuart
dc.contributor.authorGerlinger, Marco
dc.contributor.authorVarela Egocheaga, Ignacio 
dc.contributor.authorJones, David
dc.contributor.authorMarshall, John
dc.contributor.authorVoet, Thierry
dc.contributor.authorLoo, Peter van
dc.contributor.authorRassl, Doris M
dc.contributor.authorRintoul, Robert C
dc.contributor.authorJanes, Sam M
dc.contributor.authorLee, Siow-Ming
dc.contributor.authorFoster, Martin
dc.contributor.authorAhmad, Tanya
dc.contributor.authorLawrence, David
dc.contributor.authorFalzon, Mary
dc.contributor.authorCapitanio, Arrigo
dc.contributor.authorHarkins, Timothy T
dc.contributor.authorLee, Clarence C
dc.contributor.authorTom, Warrem
dc.contributor.authorTeefe, Enok
dc.contributor.authorChen, Shann-Ching
dc.contributor.authorBegum, Sharmin
dc.contributor.authorRabinowitz, Adam
dc.contributor.authorPhillimore, Benjamin
dc.contributor.authorDene, Bradley Spencer
dc.contributor.authorStamp, Gordon
dc.contributor.authorSzallasi, Zoltan
dc.contributor.authorMatthews, Nik
dc.contributor.authorStewart, Aengus
dc.contributor.authorCambell, Peter
dc.contributor.authorSvanton, Charles
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.date.accessioned2016-11-30T11:57:48Z
dc.date.available2016-11-30T11:57:48Z
dc.date.issued2014
dc.identifier.issn0036-8075
dc.identifier.issn1095-9203
dc.identifier.urihttp://hdl.handle.net/10902/9726
dc.description.abstractSpatial and temporal dissection of the genomic changes occurring during the evolution of human non-small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC.es_ES
dc.format.extent6 p.es_ES
dc.language.isoenges_ES
dc.sourceScience. 2014 Oct 10;346(6206):251-6es_ES
dc.titleSpatial and temporal diversity in genomic instability processes defines lung cancer evolutiones_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publisherVersionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636050/pdf/emss-65871.pdfes_ES
dc.rights.accessRightsopenAccesses_ES
dc.type.versionacceptedVersiones_ES


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