Modelling mutational landscapes of human cancers in vitro
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F14%3A10331264" target="_blank" >RIV/00216208:11110/14:10331264 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1038/srep04482" target="_blank" >http://dx.doi.org/10.1038/srep04482</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/srep04482" target="_blank" >10.1038/srep04482</a>
Alternative languages
Result language
angličtina
Original language name
Modelling mutational landscapes of human cancers in vitro
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FD - Oncology and haematology
OECD FORD branch
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Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2014
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Scientific Reports
ISSN
2045-2322
e-ISSN
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Volume of the periodical
4
Issue of the periodical within the volume
March
Country of publishing house
GB - UNITED KINGDOM
Number of pages
8
Pages from-to
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UT code for WoS article
000333460500003
EID of the result in the Scopus database
2-s2.0-84905382541