Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes

被引：594

作者：

Nikoloski, Gorica ^{[1
,2
]}

Langemeijer, Saskia M. C. ^{[1
,2
]}

Kuiper, Roland P. ^{[2
,3
]}

Knops, Ruth ^{[1
,2
]}

Massop, Marion ^{[1
,2
]}

Tonnissen, Evelyn R. L. T. M. ^{[1
,2
]}

van der Heijden, Adrian ^{[1
,2
]}

Scheele, Theresia N. ^{[1
,2
]}

Vandenberghe, Peter ^{[4
]}

de Witte, Theo ^{[2
,5
]}

van der Reijden, Bert A. ^{[1
,2
]}

Jansen, Joop H. ^{[1
,2
]}

机构：

[1] Radboud Univ Nijmegen, Hematol Lab, Dept Lab Med, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[2] Nijmegen Ctr Mol Life Sci, Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[4] Katholieke Univ Leuven Hosp, Lab Genet Malignant Disorders, Ctr Human Genet, Louvain, Belgium

[5] Radboud Univ Nijmegen, Dept Tumorimmunol, Med Ctr, NL-6525 ED Nijmegen, Netherlands

来源：

NATURE GENETICS | 2010年 / 42卷 / 08期

关键词：

TUMOR-SUPPRESSOR ACTIVITY; ENHANCER; COMPLEX; TET2;

D O I：

10.1038/ng.620

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：665 / 667

页数：3

共 14 条

[1]

Brunning RD., 2008, WHO CLASSIFICATION T, V4tH ed lARC, P87

[2] Role of histone H3 lysine 27 methylation in polycomb-group silencing [J].

Cao, R ;

Wang, LJ ;

Wang, HB ;

Xia, L ;

Erdjument-Bromage, H ;

Tempst, P ;

Jones, RS ;

Zhang, Y .

SCIENCE, 2002, 298 (5595) :1039-1043

[3] A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling [J].

Classen, Anne-Kathrin ;

Bunker, Brandon D. ;

Harvey, Kieran F. ;

Vaccari, Thomas ;

Bilder, David .

NATURE GENETICS, 2009, 41 (10) :1150-U139

[4] Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal polycomb sites [J].

Czermin, B ;

Melfi, R ;

McCabe, D ;

Seitz, V ;

Imhof, A ;

Pirrotta, V .

CELL, 2002, 111 (02) :185-196

[5] Mutation in TET2 in Myeloid Cancers [J].

Delhommeau, Francois ;

Dupont, Sabrina ;

Della Valle, Veronique ;

James, Chloe ;

Trannoy, Severine ;

Masse, Aline ;

Kosmider, Olivier ;

Le Couedic, Jean-Pierre ;

Robert, Fabienne ;

Alberdi, Antonio ;

Lecluse, Yann ;

Plo, Isabelle ;

Dreyfus, Francois J. ;

Marzac, Christophe ;

Casadevall, Nicole ;

Lacombe, Catherine ;

Romana, Serge P. ;

Dessen, Philippe ;

Soulier, Jean ;

Viguie, Franck ;

Fontenay, Michaela ;

Vainchenker, William ;

Bernard, Olivier A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (22) :2289-2301

[6] Nomenclature for the description of human sequence variations [J].

den Dunnen, JT ;

Antonarakis, E .

HUMAN GENETICS, 2001, 109 (01) :121-124

[7] New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes:: evidence from a core dataset of 2124 patients [J].

Haase, Detlef ;

Germing, Ulrich ;

Schanz, Julie ;

Pfeilstoecker, Michael ;

Noesslinger, Thomas ;

Hildebrandt, Barbara ;

Kundgen, Andrea ;

Luebbert, Michael ;

Kunzmann, Regina ;

Giagounidis, Aristoteles A. N. ;

Aul, Carlo ;

Truemper, Lorenz ;

Krieger, Otto ;

Stauder, Reinhard ;

Mueller, Thomas H. ;

Wimazal, Friedrich ;

Valent, Peter ;

Fonatsch, Christa ;

Steidl, Christian .

BLOOD, 2007, 110 (13) :4385-4395

[8] Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein [J].

Kuzmichev, A ;

Nishioka, K ;

Erdjument-Bromage, H ;

Tempst, P ;

Reinberg, D .

GENES & DEVELOPMENT, 2002, 16 (22) :2893-2905

[9] Acquired mutations in TET2 are common in myelodysplastic syndromes [J].

Langemeijer, Saskia M. C. ;

Kuiper, Roland P. ;

Berends, Marieke ;

Knops, Ruth ;

Aslanyan, Mariam G. ;

Massop, Marion ;

Stevens-Linders, Ellen ;

van Hoogen, Patricia ;

van Kessel, Ad Geurts ;

Raymakers, Reinier A. P. ;

Kamping, Eveline J. ;

Verhoef, Gregor E. ;

Verburgh, Estelle ;

Hagemeijer, Anne ;

Vandenberghe, Peter ;

de Witte, Theo ;

van der Reijden, Bert A. ;

Jansen, Joop H. .

NATURE GENETICS, 2009, 41 (07) :838-U102

[10] Polyhomeotic has a tumor suppressor activity mediated by repression of Notch signaling [J].

Martinez, Anne-Marie ;

Schuettengruber, Bernd ;

Sakr, Samy ;

Janic, Ana ;

Gonzalez, Cayetano ;

Cavalli, Giacomo .

NATURE GENETICS, 2009, 41 (10) :1076-U47

← 1 2 →