TY  - JOUR
AU  - Olivier, Magali
AU  - Weninger, Annette
AU  - Ardin, Maude
AU  - Huskova, Hana
AU  - Castells, Xavier
AU  - Vallée, Maxime P
AU  - McKay, James
AU  - Nedelko, Tatiana
AU  - Mühlbauer, Karl-Rudolf
AU  - Marusawa, Hiroyuki
AU  - Alexander, John
AU  - Hazelwood, Lee
AU  - Byrnes, Graham
AU  - Hollstein, Monica
AU  - Zavadil, Jiri
TI  - Modelling mutational landscapes of human cancers in vitro.
JO  - Scientific reports
VL  - 4
SN  - 2045-2322
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2017-00649
SP  - 4482
PY  - 2014
AB  - Experimental 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:24670820
C2  - pmc:PMC5259794
DO  - DOI:10.1038/srep04482
UR  - https://inrepo02.dkfz.de/record/120062
ER  -