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000120062 1001_ $$aOlivier, Magali$$b0
000120062 245__ $$aModelling mutational landscapes of human cancers in vitro.
000120062 260__ $$aLondon$$bNature Publishing Group$$c2014
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000120062 520__ $$aExperimental models that recapitulate mutational landscapes of human cancers are needed to decipher the rapidly expanding data on human somatic mutations. We demonstrate that mutation patterns in immortalised cell lines derived from primary murine embryonic fibroblasts (MEFs) exposed in vitro to carcinogens recapitulate key features of mutational signatures observed in human cancers. In experiments with several cancer-causing agents we obtained high genome-wide concordance between human tumour mutation data and in vitro data with respect to predominant substitution types, strand bias and sequence context. Moreover, we found signature mutations in well-studied human cancer driver genes. To explore endogenous mutagenesis, we used MEFs ectopically expressing activation-induced cytidine deaminase (AID) and observed an excess of AID signature mutations in immortalised cell lines compared to their non-transgenic counterparts. MEF immortalisation is thus a simple and powerful strategy for modelling cancer mutation landscapes that facilitates the interpretation of human tumour genome-wide sequencing data.
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000120062 7001_ $$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
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