Erroneous identification of APOBEC3-edited chromosomal DNA in cancer genomics View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-04-01

AUTHORS

R Suspène, V Caval, M Henry, M S Bouzidi, S Wain-Hobson, J-P Vartanian

ABSTRACT

Background:The revolution in cancer genomics shows that the dominant mutations are CG->TA transitions. The sources of these mutations are probably two host cell cytidine deaminases APOBEC3A and APOBEC3B. The former in particular can access nuclear DNA and monotonously introduce phenomenal numbers of C->T mutations in the signature 5′TpC context. These can be copied as G->A transitions in the 5′GpA context.Methods:DNA hypermutated by an APOBEC3 enzyme can be recovered by a technique called 3DPCR, which stands for differential DNA denaturation PCR. This method exploits the fact that APOBEC3-edited DNA is richer in A+T compared with the reference. We explore explicitly 3DPCR error using cloned DNA.Results:Here we show that the technique has a higher error rate compared with standard PCR and can generate DNA strands containing both C->T and G->A mutations in a 5′GpCpR context. Sequences with similar traits have been recovered from human tumour DNA using 3DPCR.Conclusions:Differential DNA denaturation PCR cannot be used to identify fixed C->T transitions in cancer genomes. Presently, the overall mutation frequency is ∼104–105 base substitutions per cancer genome, or 0.003–0.03 kb−1. By contrast, the 3DPCR error rate is of the order of 4–20 kb−1 owing to constant selection for AT DNA and PCR-mediated recombination. Accordingly, sequences recovered by 3DPCR harbouring mixed C->T and G->A mutations associated with the 5′GpC represent artefacts. More... »

PAGES

2615-2622

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2014.176

DOI

http://dx.doi.org/10.1038/bjc.2014.176

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039442540

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24691422


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