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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-05

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 ∼10(4)-10(5) 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

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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