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, 47 (7), 818-21

CTCF/cohesin-binding Sites Are Frequently Mutated in Cancer

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CTCF/cohesin-binding Sites Are Frequently Mutated in Cancer

Riku Katainen et al. Nat Genet.

Abstract

Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A•T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase ɛ (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome.

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References

    1. Bioinformatics. 2010 Dec 15;26(24):3028-34 - PubMed
    1. Cell. 2011 Dec 9;147(6):1408-19 - PubMed
    1. Nucleic Acids Res. 2013 Jan;41(2):827-41 - PubMed
    1. Cell. 2014 Dec 18;159(7):1665-80 - PubMed
    1. Science. 2014 Dec 12;346(6215):1373-7 - PubMed

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