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.
This is a preview of subscription content, access via your institution
Access options
Similar content being viewed by others
References
Brunning, R.D. et al. in WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (eds. Swerdlow, S.H. et al.) 87–104 (World Health Organization, Geneva, 2008).
Haase, D. et al. Blood 110, 4385–4395 (2007).
Langemeijer, S.M.C. et al. Nat. Genet. 41, 838–842 (2009).
Delhommeau, F. et al. N. Engl. J. Med. 360, 2289–2301 (2009).
Den Dunnen, J.T. & Antonarakis, S.E. Hum. Genet. 109, 121–124 (2001).
Tahiliani, M. et al. Science 324, 930–935 (2009).
Cao, R. et al. Science 298, 1039–1043 (2002).
Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P. & Reinberg, D. Genes Dev. 16, 2893–2905 (2002).
Czermin, B. et al. Cell 111, 185–196 (2002).
Muller, J. et al. Cell 111, 197–208 (2002).
Morin, R.D. et al. Nat. Genet. 42, 181–185 (2010).
Classen, A.K., Bunker, B.D., Harvey, K.F., Vaccari, T. & Bilder, D. Nat. Genet. 41, 1150–1155 (2009).
Martinez, A.M. et al. Nat. Genet. 41, 1076–1082 (2009).
Simon, J.A. & Lange, C.A. Mutat. Res. 647, 21–29 (2008).
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.
Author information
Authors and Affiliations
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
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Text and Figures (download PDF )
Supplementary Figures 1–8, Supplementary Tables 1–3 and Supplementary Methods (PDF 1545 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/ng.620
