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.

  • Brief Communication
  • Published:

Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas

Abstract

To identify somatic mutations in pediatric diffuse intrinsic pontine glioma (DIPG), we performed whole-genome sequencing of DNA from seven DIPGs and matched germline tissue and targeted sequencing of an additional 43 DIPGs and 36 non-brainstem pediatric glioblastomas (non-BS-PGs). We found that 78% of DIPGs and 22% of non-BS-PGs contained a mutation in H3F3A, encoding histone H3.3, or in the related HIST1H3B, encoding histone H3.1, that caused a p.Lys27Met amino acid substitution in each protein. An additional 14% of non-BS-PGs had somatic mutations in H3F3A causing a p.Gly34Arg alteration.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Recurrent somatic mutations in H3F3A and HIST1H3B.

Similar content being viewed by others

References

  1. Broniscer, A. & Gajjar, A. Oncologist 9, 197–206 (2004).

    Article  PubMed  Google Scholar 

  2. Paugh, B.S. et al. J. Clin. Oncol. 29, 3999–4006 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Paugh, B.S. et al. J. Clin. Oncol. 28, 3061–3068 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Barrow, J. et al. Neuro. Oncol. 13, 212–222 (2011).

    Article  CAS  PubMed  Google Scholar 

  5. Bax, D.A. et al. Clin. Cancer Res. 16, 3368–3377 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zarghooni, M. et al. J. Clin. Oncol. 28, 1337–1344 (2010).

    Article  CAS  PubMed  Google Scholar 

  7. Qu, H.Q. et al. Neuro. Oncol. 12, 153–163 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Warren, K.E. et al. Neuro. Oncol. published online (7 November 2011), doi:10.1093/neuonc/nor190.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Campos, E.I. & Reinberg, D. Annu. Rev. Genet. 43, 559–599 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. Barski, A. et al. Cell 129, 823–837 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Reynolds, N. et al. EMBO J. published online (2 December 2011), doi:10.1038/emboj.2011.431.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Goldberg, A.D. et al. Cell 140, 678–691 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Füllgrabe, J., Kavanagh, E. & Joseph, B. Oncogene 30, 3391–3403 (2011).

    Article  PubMed  Google Scholar 

  14. Parsons, D.W. et al. Science 321, 1807–1812 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank X. Zhu and A. Diaz for assistance with PCR reactions, J. Partridge for helpful discussions, the Hartwell Center of Biotechnology and Bioinformatics at St. Jude Children's Research Hospital and Beckman Coulter Genomics. This work was supported by the St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project and the American Lebanese Syrian Associated Charities (ALSAC) of St. Jude Children's Research Hospital and by grants from the US National Institutes of Health (NIH) (CA096832), the Sydney Schlobohm Chair of Research from the National Brain Tumor Society, the Cure Starts Now Foundation, the Smile for Sophie Forever Foundation, Tyler's Treehouse Foundation, the Musicians Against Childhood Cancer and the Noyes Brain Tumor Foundation.

Author information

Authors and Affiliations

Consortia

Contributions

S.J.B., T.A.M., B.S.P., C.Q., J.R.D., E.R.M. and R.K.W. designed the experiments. A.B. and A.G. provided samples and clinical data. D.W.E. performed histopathological analyses. D.W.E., M.A.D., C.G.M., R.J.G. and J.R.D. provided data from other tumor types. G.W. and C.L. analyzed the whole-genome sequence data. T.A.M., B.S.P. and Junyuan Zhang performed validation experiments. J.B. analyzed the Sanger sequencing data for the validation cohort. R.H. performed structural modeling for the mutations. L.D. and Jinghui Zhang supervised the data analysis. G.W., M.P., Jinghui Zhang and S.J.B. prepared the tables and figures. J.R.D., Jinghui Zhang and S.J.B. wrote the manuscript.

Corresponding authors

Correspondence to Richard K Wilson, James R Downing, Jinghui Zhang or Suzanne J Baker.

Ethics declarations

Competing interests

The author declare no competing financial interests.

Additional information

A full list of consortium members is provided in the Supplementary Note.

Supplementary information

Supplementary Text and Figures

Supplementary Note, Supplementary Methods, Supplementary Tables 1–3 and Supplementary Figure 1 (PDF 496 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44, 251–253 (2012). https://doi.org/10.1038/ng.1102

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.1102

This article is cited by

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