Erroneous identification of APOBEC3-edited chromosomal DNA in cancer genomics
| Autor: | Caval, Mohamed S. Bouzidi, Jean-Pierre Vartanian, Michel Henry, Rodolphe Suspène, Simon Wain-Hobson |
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| Přispěvatelé: | Rétrovirologie Moléculaire, Institut Pasteur [Paris] (IP), This work was supported by grants from the Institut Pasteur, INCa and the CNRS. VC and MSB were supported by OSEO and the Ligue Nationale Contre le Cancer. |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
MESH: Neoplasm Proteins
CD4-Positive T-Lymphocytes Cancer Research [SDV]Life Sciences [q-bio] MESH: beta Catenin Cytidine medicine.disease_cause Nucleic Acid Denaturation Genome Polymerase Chain Reaction law.invention Cytosine Deaminase chemistry.chemical_compound MESH: Liver Neoplasms law APOBEC Deaminases APOBEC3A MESH: Carcinoma Hepatocellular Polymerase chain reaction Cells Cultured beta Catenin Genetics Recombination Genetic Mutation Liver Neoplasms MESH: APOBEC Deaminases Temperature MESH: CD4-Positive T-Lymphocytes APOBEC3 DNA Neoplasm MESH: Temperature MESH: Hepatitis C Chronic Nuclear DNA Neoplasm Proteins Oncology MESH: Recombination Genetic MESH: Interferon-alpha MESH: Cytidine MESH: Cells Cultured MESH: Mutation Carcinoma Hepatocellular MESH: Hepatitis B Chronic MESH: DNA Neoplasm Context (language use) Genomics MESH: Nucleic Acid Denaturation Biology MESH: Phytohemagglutinins Hepatitis B Chronic Cytidine Deaminase medicine Humans 3DPCR Phytohemagglutinins MESH: Cytidine Deaminase cancer genomics MESH: Humans MESH: Cytosine Deaminase hypermutation Interferon-alpha MESH: Interleukin-2 MESH: Polymerase Chain Reaction Genetics and Genomics Hepatitis C Chronic chemistry Interleukin-2 DNA |
| Zdroj: | British Journal of Cancer British Journal of Cancer, 2014, 110 (10), pp.2615-2622. ⟨10.1038/bjc.2014.176⟩ |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.2014.176⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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