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PMID: 19330029 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer.

Nature genetics ·Vol. 41 ·No. 5 ·2009-05-00 ·Pages 521-3

van Haaften G, Dalgliesh GL, Davies H, Chen L, Bignell G, Greenman C, Edkins S, Hardy C, O'Meara S, Teague J, Butler A, Hinton J, Latimer C, Andrews J, Barthorpe S, Beare D, Buck G, Campbell PJ, Cole J, Forbes S, Jia M, Jones D, Kok CY, Leroy C, Lin ML, McBride DJ, Maddison M, Maquire S, McLay K, Menzies A, Mironenko T, Mulderrig L, Mudie L, Pleasance E, Shepherd R, Smith R, Stebbings L, Stephens P, Tang G, Tarpey PS, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Collins VP, Ichimura K, Law S, Wong J, Yuen ST, Leung SY, Tonon G, DePinho RA, Tai YT, Anderson KC, Kahnoski RJ, Massie A, Khoo SK, Teh BT, Stratton MR, Futreal PA

Abstract

Somatically acquired epigenetic changes are present in many cancers. Epigenetic regulation is maintained via post-translational modifications of core histones. Here, we describe inactivating somatic mutations in the histone lysine demethylase gene UTX, pointing to histone H3 lysine methylation deregulation in multiple tumor types. UTX reintroduction into cancer cells with inactivating UTX mutations resulted in slowing of proliferation and marked transcriptional changes. These data identify UTX as a new human cancer gene.

MeSH Terms
Epigenesis, Genetic Humans Jumonji Domain-Containing Histone Demethylases Mutation Neoplasms/enzymology,genetics Oxidoreductases, N-Demethylating/genetics
Chemicals
Jumonji Domain-Containing Histone Demethylases KDM6B protein, human Oxidoreductases, N-Demethylating
Authors & Affiliations
62 authors, click to expand affiliations / ORCID
van Haaften Gijs
Wellcome Trust Sanger Institute, Hinxton, UK.
Dalgliesh Gillian L
Davies Helen
Chen Lina
Bignell Graham
Greenman Chris
Edkins Sarah
Hardy Claire
O'Meara Sarah
Teague Jon
Butler Adam
Hinton Jonathan
Latimer Calli
Andrews Jenny
Barthorpe Syd
Beare Dave
Buck Gemma
Campbell Peter J
Cole Jennifer
Forbes Simon
Jia Mingming
Jones David
Kok Chai Yin
Leroy Catherine
Lin Meng-Lay
McBride David J
Maddison Mark
Maquire Simon
McLay Kirsten
Menzies Andrew
Mironenko Tatiana
Mulderrig Lee
Mudie Laura
Pleasance Erin
Shepherd Rebecca
Smith Raffaella
Stebbings Lucy
Stephens Philip
Tang Gurpreet
Tarpey Patrick S
Turner Rachel
Turrell Kelly
Varian Jennifer
West Sofie
Widaa Sara
Wray Paul
Collins V Peter
Ichimura Koichi
Law Simon
Wong John
Yuen Siu Tsan
Leung Suet Yi
Tonon Giovanni
DePinho Ronald A
Tai Yu-Tzu
Anderson Kenneth C
Kahnoski Richard J
Massie Aaron
Khoo Sok Kean
Teh Bin Tean
Stratton Michael R
Futreal P Andrew
References (15)
15 references, click to expand
  1. Chromatin modifications and their function.
    Cell. 2007 Feb 23;128(4):693-705 PMID: 17320507
  2. UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development.
    Nature. 2007 Oct 11;449(7163):731-4 PMID: 17713478
  3. Multiple-myeloma-related WHSC1/MMSET isoform RE-IIBP is a histone methyltransferase with transcriptional repression activity.
    Mol Cell Biol. 2008 Mar;28(6):2023-34 PMID: 18172012
  4. Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination.
    Science. 2007 Oct 19;318(5849):447-50 PMID: 17761849
  5. A histone H3 lysine 27 demethylase regulates animal posterior development.
    Nature. 2007 Oct 11;449(7163):689-94 PMID: 17851529
  6. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions.
    Genes Dev. 2006 May 1;20(9):1123-36 PMID: 16618801
  7. The human myeloma cell line LP-1: a versatile model in which to study early plasma-cell differentiation and c-myc activation.
    Blood. 1989 Mar;73(4):1020-7 PMID: 2784066
  8. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer.
    Nat Genet. 2007 Feb;39(2):232-6 PMID: 17200670
  9. Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases.
    Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18439-44 PMID: 18003914
  10. The UTX gene escapes X inactivation in mice and humans.
    Hum Mol Genet. 1998 Apr;7(4):737-42 PMID: 9499428
  11. The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor.
    Blood. 2008 Mar 15;111(6):3145-54 PMID: 18156491
  12. Correlation of chromosomal aberrations in a myeloma cell line with tumorigenicity in nude mice.
    Blut. 1981 Aug;43(2):93-7 PMID: 7260411
  13. Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells.
    Cell Stem Cell. 2007 Sep 13;1(3):299-312 PMID: 18371364
  14. Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth.
    Mol Cell Biol. 2007 Mar;27(5):1889-903 PMID: 17178841
  15. An X chromosome gene, WTX, is commonly inactivated in Wilms tumor.
    Science. 2007 Feb 2;315(5812):642-5 PMID: 17204608
Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.349
Published
2009-05-00
Epub
2009-00-29
Pages
521-3
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2873835
Subset
IM
Grants
Wellcome Trust · 077012 · United Kingdom
Wellcome Trust · 088340 · United Kingdom
External Links
PubMed source DOI: 10.1038/ng.349 PMC Full Text View journal details
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