Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Avalanching mutations in biallelic mismatch repair deficiency syndrome

Nature Genetics volume 47, pages 194–196 (2015)Cite this article

Subjects

Tumors from pediatric patients generally contain relatively few somatic mutations. A new study reports a striking exception in individuals in whom biallelic germline deficiency for mismatch repair is compounded by somatic loss of function in DNA proofreading polymerases, resulting in 'ultra-hypermutated' malignant brain tumors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Mutation accumulation and cancer development in patients with bMMRD.

Marina Corral Spence/Nature Publishing Group

References

  1. Wimmer, K. et al. J. Med. Genet. 51, 355–365 (2014).

    Article  CAS  Google Scholar 

  2. Shlien, A. et al. Nat. Genet. 47, 257–262 (2015).

    Article  CAS  Google Scholar 

  3. Schlussel, A.T. et al. J. Gastrointest. Oncol. 5, 326–335 (2014).

    PubMed  PubMed Central  Google Scholar 

  4. Palles, C. et al. Nat. Genet. 45, 136–144 (2013).

    Article  CAS  Google Scholar 

  5. Wang, Q. et al. Cancer Res. 59, 294–297 (1999).

    CAS  PubMed  Google Scholar 

  6. Ricciardone, M.D. et al. Cancer Res. 59, 290–293 (1999).

    CAS  Google Scholar 

  7. Cancer Genome Atlas Network. Nature 487, 330–337 (2012).

  8. Yoshida, R. et al. Eur. J. Hum. Genet. 19, 320–325 (2011).

    Article  Google Scholar 

  9. Zhao, S. et al. Proc. Natl. Acad. Sci. USA 110, 2916–2921 (2013).

    Article  CAS  Google Scholar 

  10. Church, D.N. et al. Hum. Mol. Genet. 22, 2820–2828 (2013).

    Article  CAS  Google Scholar 

  11. Kandoth, C. et al. Nature 497, 67–73 (2013).

    Article  Google Scholar 

  12. Alexandrov, L.B. et al. Nature 500, 415–421 (2013).

    Article  CAS  Google Scholar 

  13. Williams, L.N., Herr, A.J. & Preston, B.D. Genetics 193, 751–770 (2013).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Joshua J. Waterfall and Paul S. Meltzer are at the Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.,

    Joshua J Waterfall & Paul S Meltzer

Authors
  1. Joshua J Waterfall
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul S Meltzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul S Meltzer.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Waterfall, J., Meltzer, P. Avalanching mutations in biallelic mismatch repair deficiency syndrome. Nat Genet 47, 194–196 (2015). https://doi.org/10.1038/ng.3227

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.3227

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer