Scientific Publications

An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers.

Publication TypeJournal Article
AuthorsRoberts, SA, Lawrence MS, Klimczak LJ, Grimm SA, Fargo D., Stojanov P., Kiezun A., Kryukov GV, Carter SL, Saksena G., Harris S., Shah RR, Resnick MA, Getz G., and Gordenin DA
AbstractRecent studies indicate that a subclass of APOBEC cytidine deaminases, which convert cytosine to uracil during RNA editing and retrovirus or retrotransposon restriction, may induce mutation clusters in human tumors. We show here that throughout cancer genomes APOBEC-mediated mutagenesis is pervasive and correlates with APOBEC mRNA levels. Mutation clusters in whole-genome and exome data sets conformed to the stringent criteria indicative of an APOBEC mutation pattern. Applying these criteria to 954,247 mutations in 2,680 exomes from 14 cancer types, mostly from The Cancer Genome Atlas (TCGA), showed a significant presence of the APOBEC mutation pattern in bladder, cervical, breast, head and neck, and lung cancers, reaching 68% of all mutations in some samples. Within breast cancer, the HER2-enriched subtype was clearly enriched for tumors with the APOBEC mutation pattern, suggesting that this type of mutagenesis is functionally linked with cancer development. The APOBEC mutation pattern also extended to cancer-associated genes, implying that ubiquitous APOBEC-mediated mutagenesis is carcinogenic.
Year of Publication2013
JournalNature genetics
Volume45
Issue9
Pages970-6
Date Published (YYYY/MM/DD)2013/08/28
ISSN Number1061-4036
DOI10.1038/ng.2702
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/23852170?dopt=Abstract