000120062 001__ 120062 000120062 005__ 20240228135009.0 000120062 0247_ $$2doi$$a10.1038/srep04482 000120062 0247_ $$2pmid$$apmid:24670820 000120062 0247_ $$2pmc$$apmc:PMC5259794 000120062 0247_ $$2altmetric$$aaltmetric:2216373 000120062 037__ $$aDKFZ-2017-00649 000120062 041__ $$aeng 000120062 082__ $$a000 000120062 1001_ $$aOlivier, Magali$$b0 000120062 245__ $$aModelling mutational landscapes of human cancers in vitro. 000120062 260__ $$aLondon$$bNature Publishing Group$$c2014 000120062 3367_ $$2DRIVER$$aarticle 000120062 3367_ $$2DataCite$$aOutput Types/Journal article 000120062 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1490777778_9393 000120062 3367_ $$2BibTeX$$aARTICLE 000120062 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000120062 3367_ $$00$$2EndNote$$aJournal Article 000120062 520__ $$aExperimental models that recapitulate mutational landscapes of human cancers are needed to decipher the rapidly expanding data on human somatic mutations. We demonstrate that mutation patterns in immortalised cell lines derived from primary murine embryonic fibroblasts (MEFs) exposed in vitro to carcinogens recapitulate key features of mutational signatures observed in human cancers. In experiments with several cancer-causing agents we obtained high genome-wide concordance between human tumour mutation data and in vitro data with respect to predominant substitution types, strand bias and sequence context. Moreover, we found signature mutations in well-studied human cancer driver genes. To explore endogenous mutagenesis, we used MEFs ectopically expressing activation-induced cytidine deaminase (AID) and observed an excess of AID signature mutations in immortalised cell lines compared to their non-transgenic counterparts. MEF immortalisation is thus a simple and powerful strategy for modelling cancer mutation landscapes that facilitates the interpretation of human tumour genome-wide sequencing data. 000120062 536__ $$0G:(DE-HGF)POF3-313$$a313 - Cancer risk factors and prevention (POF3-313)$$cPOF3-313$$fPOF III$$x0 000120062 588__ $$aDataset connected to CrossRef, PubMed, 000120062 7001_ $$0P:(DE-He78)b787d22d9cb06342658bf546039117bc$$aWeninger, Annette$$b1$$udkfz 000120062 7001_ $$aArdin, Maude$$b2 000120062 7001_ $$aHuskova, Hana$$b3 000120062 7001_ $$aCastells, Xavier$$b4 000120062 7001_ $$aVallée, Maxime P$$b5 000120062 7001_ $$aMcKay, James$$b6 000120062 7001_ $$0P:(DE-HGF)0$$aNedelko, Tatiana$$b7 000120062 7001_ $$0P:(DE-He78)0a78151e49e9c847ad9e913a5c2b0ffe$$aMühlbauer, Karl-Rudolf$$b8$$udkfz 000120062 7001_ $$aMarusawa, Hiroyuki$$b9 000120062 7001_ $$aAlexander, John$$b10 000120062 7001_ $$aHazelwood, Lee$$b11 000120062 7001_ $$aByrnes, Graham$$b12 000120062 7001_ $$0P:(DE-He78)f3bec70c95e9e3dce0f39d54b3843118$$aHollstein, Monica$$b13$$udkfz 000120062 7001_ $$aZavadil, Jiri$$b14 000120062 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/srep04482$$gVol. 4$$p4482$$tScientific reports$$v4$$x2045-2322$$y2014 000120062 909CO $$ooai:inrepo02.dkfz.de:120062$$pVDB 000120062 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)b787d22d9cb06342658bf546039117bc$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ 000120062 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ 000120062 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)0a78151e49e9c847ad9e913a5c2b0ffe$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ 000120062 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f3bec70c95e9e3dce0f39d54b3843118$$aDeutsches Krebsforschungszentrum$$b13$$kDKFZ 000120062 9131_ $$0G:(DE-HGF)POF3-313$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vCancer risk factors and prevention$$x0 000120062 9141_ $$y2014 000120062 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bSCI REP-UK : 2015 000120062 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000120062 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000120062 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000120062 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal 000120062 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ 000120062 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ 000120062 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000120062 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000120062 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000120062 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000120062 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences 000120062 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record 000120062 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000120062 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bSCI REP-UK : 2015 000120062 9201_ $$0I:(DE-He78)C016-20160331$$kC016$$lGenetische Veränderungen bei der Karzinogenese$$x0 000120062 980__ $$ajournal 000120062 980__ $$aVDB 000120062 980__ $$aI:(DE-He78)C016-20160331 000120062 980__ $$aUNRESTRICTED