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.

Avalanching mutations in biallelic mismatch repair deficiency syndrome

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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

Marina Corral Spence/Nature Publishing Group

References

  1. 1

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

    CAS  Article  Google Scholar 

  2. 2

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

    CAS  Article  Google Scholar 

  3. 3

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

    PubMed  PubMed Central  Google Scholar 

  4. 4

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

    CAS  Article  Google Scholar 

  5. 5

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

    CAS  PubMed  Google Scholar 

  6. 6

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

    CAS  Google Scholar 

  7. 7

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

  8. 8

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

    Article  Google Scholar 

  9. 9

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

    CAS  Article  Google Scholar 

  10. 10

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

    CAS  Article  Google Scholar 

  11. 11

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

    Article  Google Scholar 

  12. 12

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

    CAS  Article  Google Scholar 

  13. 13

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

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

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

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

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing