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Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes

Nature Genetics volume 42, pages 665–667 (2010)Cite this article

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Abstract

In myelodysplastic syndromes (MDS), deletions of chromosome 7 or 7q are common and correlate with a poor prognosis. The relevant genes on chromosome 7 are unknown. We report here that EZH2, located at 7q36.1, is frequently targeted in MDS. Analysis of EZH2 deletions, missense and frameshift mutations strongly suggests that EZH2 is a tumor suppressor. As EZH2 functions as a histone methyltransferase, abnormal histone modification may contribute to epigenetic deregulation in MDS.

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Figure 1: EZH2 is recurrently affected in individuals with MDS.

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Acknowledgements

We thank R. Woestenenk and E. Kamping for technical assistance. This work was supported by grants from the Dutch Organization for Scientific Research (NWO, 92003420) and the Stichting Vanderes (07-183). P.V. is a clinical investigator of Fonds Wetenschappelijk Onderzoek Vlaanderen.

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Author notes

  1. Gorica Nikoloski and Saskia M C Langemeijer: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands

    Gorica Nikoloski, Saskia M C Langemeijer, Ruth Knops, Marion Massop, Evelyn R L T M Tönnissen, Adrian van der Heijden, Theresia N Scheele, Bert A van der Reijden & Joop H Jansen

  2. Department of Human Genetics, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands

    Roland P Kuiper

  3. Laboratory for Genetics of Malignant Disorders, Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium

    Peter Vandenberghe

  4. Department of Tumorimmunology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands

    Theo de Witte

Authors
  1. Gorica Nikoloski
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  2. Saskia M C Langemeijer
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Contributions

G.N., S.M.C.L., R.P.K., T.d.W., B.A.v.d.R. and J.H.J. designed the experiments. G.N., S.M.C.L., R.K., M.M., E.R.L.T.M.T., A.v.d.H., T.N.S., P.V. and T.d.W. provided subject material and clinical data. S.M.C.L. and R.P.K. performed and analyzed the SNP arrays. G.N., E.R.L.T.M.T., M.M., A.v.d.H. and T.N.S. performed sequence analysis and allelic discrimination assays. G.N. and J.H.J. wrote the paper.

Corresponding author

Correspondence to Joop H Jansen.

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The authors declare no competing financial interests.

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Supplementary Figures 1–8, Supplementary Tables 1–3 and Supplementary Methods (PDF 1545 kb)

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Nikoloski, G., Langemeijer, S., Kuiper, R. et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet 42, 665–667 (2010). https://doi.org/10.1038/ng.620

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