5-hydroxymethylcytosine marks regions with reduced mutation frequency in human DNA

Abstract

CpG dinucleotides are the main mutational hot-spot in most cancers. The characteristic elevated C>T mutation rate in CpG sites has been related to 5-methylcytosine (5mC), an epigenetically modified base which resides in CpGs and plays a role in transcription silencing. In brain nearly a third of 5mCs have recently been found to exist in the form of 5-hydroxymethylcytosine (5hmC), yet the effect of 5hmC on mutational processes is still poorly understood. Here we show that 5hmC is associated with an up to 53% decrease in the frequency of C>T mutations in a CpG context compared to 5mC. Tissue specific 5hmC patterns in brain, kidney and blood correlate with lower regional CpG>T mutation frequency in cancers originating in the respective tissues. Together our data reveal global and opposing effects of the two most common cytosine modifications on the frequency of cancer causing somatic mutations in different cell types.

Article and author information

Author details

  1. Marketa Tomkova

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael McClellan

    Ludwig Cancer Research Oxford, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Skirmantas Kriaucionis

    Ludwig Cancer Research Oxford, University of Oxford, Oxford, United Kingdom
    For correspondence
    skirmantas.kriaucionis@ludwig.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  4. Benjamin Schuster-Boeckler

    Ludwig Cancer Research Oxford, University of Oxford, Oxford, United Kingdom
    For correspondence
    benjamin.schuster-boeckler@ludwig.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Daniel Zilberman, University of California, Berkeley, United States

Publication history

  1. Received: April 20, 2016
  2. Accepted: May 13, 2016
  3. Accepted Manuscript published: May 16, 2016 (version 1)
  4. Accepted Manuscript updated: May 17, 2016 (version 2)
  5. Accepted Manuscript updated: May 17, 2016 (version 3)
  6. Version of Record published: July 4, 2016 (version 4)

Copyright

© 2016, Tomkova et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Marketa Tomkova
  2. Michael McClellan
  3. Skirmantas Kriaucionis
  4. Benjamin Schuster-Boeckler
(2016)
5-hydroxymethylcytosine marks regions with reduced mutation frequency in human DNA
eLife 5:e17082.
https://doi.org/10.7554/eLife.17082

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