Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer
Open accessAbstract
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.
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Inactivating mutations and/or reduced expression of JmjC histone demethylases including JARID1C, UTX and JHDM1B/FBXL10 occur in renal cell carcinomas, multiple myeloma, glioblastoma multiforme and several other cancers.
“Interestingly, inactivating mutations and/or reduced expression of JmjC histone demethylases including JARID1C (Dalgliesh et al, 2010), UTX (van Haaften et al, 2009) and JHDM1B/FBXL10 (Frescas et al, 2007), occur in RCCs, multiple myeloma, glioblastoma multiforme and several other cancers.”
From The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases (2011) · cites this paper as van Haaften et al, 2009
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Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883 · see citing works
Chen, X., Xiu, M., Xing, J., Yu, S., Min, D., & Guo, F. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479439 · Cited by 5,759 · see citing works
UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development
Agger, K., Cloos, P. A., Christensen, J. F., Pasini, D., Rose, S., Rappsilber, J., Issaeva, I., Canaani, E., Salcini, A. E., & Helin, K. (2007) · Nature · doi:10.1038/nature06145 · Cited by 1,392 · see citing works
Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitionsPreprint
Bracken, A. P., Dietrich, N., Pasini, D., Hansen, K. H., & Helin, K. (2006) · Genes & Development · doi:10.1101/gad.381706 · Cited by 1,258 · see citing works
Schlesinger, Y., Straussman, R., Keshet, I., Farkash, S., Hecht, M., Zimmerman, J., Eden, E., Yakhini, Z., Ben-Shushan, E., Reubinoff, B. E., et al. (2007) · Nature Genetics · doi:10.1038/ng1950 · Cited by 1,226 · see citing works
A histone H3 lysine 27 demethylase regulates animal posterior development
Lan, F., Bayliss, P. E., Rinn, J. L., Whetstine, J. R., Wang, J. K., Chen, S., Iwase, S., Alpatov, R., Issaeva, I., Canaani, E., et al. (2007) · Nature · doi:10.1038/nature06192 · Cited by 782 · see citing works
Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination
Lee, M. G., Villa, R., Trojer, P., Norman, J. A., Yan, K.-P., Reinberg, D., Croce, L. D., & Shiekhattar, R. (2007) · Science · doi:10.1126/science.1149042 · Cited by 772 · see citing works
Whole-Genome Analysis of Histone H3 Lysine 4 and Lysine 27 Methylation in Human Embryonic Stem Cells
Pan, G., Tian, S., Nie, J., Yang, C., Ruotti, V., Wei, H., Jonsdottir, G. A., Stewart, R., & Thomson, J. A. (2007) · Cell Stem Cell · doi:10.1016/j.stem.2007.08.003 · Cited by 711 · see citing works
Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases
Hong, S., Cho, Y., Yu, L., Yu, H., Veenstra, T. D., & Ge, K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707292104 · Cited by 700 · see citing works
Issaeva, I., Zonis, Y. A., Rozovskaia, T., Orlovsky, K., Croce, C. M., Nakamura, T., Mazo, A., Eisenbach, L., & Canaani, E. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01506-06 · Cited by 380 · see citing works
An X Chromosome Gene, WTX , Is Commonly Inactivated in Wilms Tumor
Rivera, M. N., Kim, W. J., Wells, J. M., Driscoll, D. R., Brannigan, B. W., Han, M., Kim, J. C., Feinberg, A. P., Gerald, W. L., Vargas, S. O., et al. (2007) · Science · doi:10.1126/science.1137509 · Cited by 339 · see citing works
The UTX gene escapes X inactivation in mice and humans
Greenfield, A. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.4.737 · Cited by 276 · see citing works
Marango, J., Shimoyama, M., Nishio, H., Meyer, J. A., Min, D.-J., Sirulnik, A., Martinez-Martinez, Y., Chesi, M., Bergsagel, P. L., Zhou, M., et al. (2007) · Blood · doi:10.1182/blood-2007-06-092122 · Cited by 198 · see citing works
Kim, J., Kee, H. J., Choe, N., Kim, S., Eom, G.-H., Baek, H. J., Kook, H., Kook, H., & Seo, S. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.02130-07 · Cited by 98 · see citing works
Pegoraro, L., Malavasi, F., Bellone, G., et al. (1989) · Blood · doi:10.1182/blood.v73.4.1020.1020 · Cited by 60 · see citing works
Correlation of chromosomal aberrations in a myeloma cell line with tumorigenicity in nude mice
Kirchner, H. H., Fonatsch, C., Schaadt, M., et al. (1981) · Annals of Hematology · doi:10.1007/bf00320467 · Cited by 10 · see citing works
Flagged first, then by citations
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Regulation of chromatin by histone modifications
Bannister, A. J., & Kouzarides, T. (2011) · Cell Research · doi:10.1038/cr.2011.22 · Cited by 6,012 · see citing works
Cancer epigenetics: from mechanism to therapy
Dawson, M. A., & Kouzarides, T. (2012) · Cell · doi:10.1016/j.cell.2012.06.013 · Cited by 3,203 · see citing works
A decade of exploring the cancer epigenome—biological and translational implications
Baylin, S. B., & Jones, P. A. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3130 · Cited by 2,871 · see citing works
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Greer, E. L., & Shi, Y. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3173 · Cited by 2,241 · see citing works
IDH mutation impairs histone demethylation and results in a block to cell differentiation
Lu, C., Ward, P. S., Kapoor, G. S., Rohle, D., Turcan, S., Abdel-Wahab, O., Edwards, C. R., Khanin, R., Figueroa, M. E., Melnick, A., et al. (2012) · Nature · doi:10.1038/nature10860 · Cited by 1,985 · see citing works
EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations
McCabe, M. T., Ott, H. M., Ganji, G., Korenchuk, S., Thompson, C., Van Aller, G. S., Liu, Y., Graves, A. P., III, A. D. P., Diaz, E., et al. (2012) · Nature · doi:10.1038/nature11606 · Cited by 1,786 · see citing works
Kim, K. H., & Roberts, C. W. M. (2016) · Nature Medicine · doi:10.1038/nm.4036 · Cited by 1,471 · see citing works
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation
Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., Figueroa, M. E., Vasanthakumar, A., Patel, J., Zhao, X., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.001 · Cited by 1,339 · see citing works
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
Dalgliesh, G. L., Furge, K., Greenman, C., Chen, L., Bignell, G., Butler, A., Davies, H., Edkins, S., Hardy, C., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08672 · Cited by 1,173 · see citing works
Self-citationShilatifard, A. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-051710-134100 · Cited by 1,091 · see citing works
Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders
Ernst, T., Chase, A. J., Score, J., Hidalgo-Curtis, C. E., Bryant, C., Jones, A. V., Waghorn, K., Zoi, K., Ross, F. M., Reiter, A., et al. (2010) · Nature Genetics · doi:10.1038/ng.621 · Cited by 1,139 · see citing works
The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases
Chowdhury, R., Yeoh, K. K., Tian, Y., Hillringhaus, L., Bagg, E. A., Rose, N. R., Leung, I. K. H., Li, X. S., Woon, E. C. Y., Yang, M., et al. (2011) · The EMBO Reports · doi:10.1038/embor.2011.43 · Cited by 1,035 · see citing works
Influence of Metabolism on Epigenetics and Disease
Kaelin, W. G., & McKnight, S. L. (2013) · Cell · doi:10.1016/j.cell.2013.03.004 · Cited by 920 · see citing works
Dissecting the genomic complexity underlying medulloblastoma
Jones, D. T. W., Jäger, N., Kool, M., Zichner, T., Hutter, B., Sultan, M., Cho, Y.-J., Pugh, T. J., Hovestadt, V., Stütz, A. M., et al. (2012) · Nature · doi:10.1038/nature11284 · Cited by 839 · see citing works
Self-citationPolakis, P. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008052 · Cited by 847 · see citing works
A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells
Knutson, S. K., Wigle, T. J., Warholic, N. M., Sneeringer, C. J., Allain, C. J., Klaus, C. R., Sacks, J. D., Raimondi, A., Majer, C. R., Song, J., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1084 · Cited by 776 · see citing works
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Shanbhag, N. M., Rafalska-Metcalf, I. U., Balane-Bolivar, C., Janicki, S. M., & Greenberg, R. A. (2010) · Cell · doi:10.1016/j.cell.2010.04.038 · Cited by 737 · see citing works
Epigenetic reprogramming in cancer
Suvà, M. L., Riggi, N., & Bernstein, B. E. (2013) · Science · doi:10.1126/science.1230184 · Cited by 706 · see citing works
Ko, M., Bandukwala, H. S., An, J., Lamperti, E. D., Thompson, E. C., Hastie, R., Tsangaratou, A., Rajewsky, K., Koralov, S. B., & Rao, A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112317108 · Cited by 616 · see citing works
The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset
Ceol, C. J., Houvras, Y., Jane-Valbuena, J., Bilodeau, S., Orlando, D. A., Battisti, V., Fritsch, L., Lin, W. M., Hollmann, T. J., Ferré, F., et al. (2011) · Nature · doi:10.1038/nature09806 · Cited by 542 · see citing works
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Hamamoto, R., Saloura, V., & Nakamura, Y. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3884 · Cited by 376 · see citing works
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Laugesen, A., & Helin, K. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.05.006 · Cited by 352 · see citing works
Andricovich, J., Perkail, S., Kai, Y., Casasanta, N., Peng, W., & Tzatsos, A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.02.003 · Cited by 320 · see citing works
<scp>l</scp> -2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer
Shim, E.-H., Livi, C. B., Rakheja, D., Tan, J., Benson, D., Parekh, V., Kho, E.-Y., Ghosh, A. P., Kirkman, R., Velu, S., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0696 · Cited by 280 · see citing works
Marked for death: Targeting epigenetic changes in cancer
Pfister, S. X., & Ashworth, A. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.256 · Cited by 288 · see citing works
X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner
Welstead, G. G., Creyghton, M. P., Bilodeau, S., Cheng, A. W., Markoulaki, S., Young, R. A., & Jaenisch, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210787109 · Cited by 194 · see citing works
The emerging role of fumarate as an oncometabolite
Yang, M., Soga, T., Pollard, P. J., & Adam, J. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00085 · Cited by 189 · see citing works
Pereira, F., Barbáchano, A., Silva, J., Bonilla, F., Campbell, M. J., Muñoz, A., & Larriba, M. J. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr399 · Cited by 177 · see citing works
Rocquain, J., Carbuccia, N., Trouplin, V., Raynaud, S., Murati, A., Nezri, M., Tadrist, Z., Olschwang, S., Vey, N., Birnbaum, D., et al. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-401 · Cited by 171 · see citing works
Pacheco-Pinedo, E. C., Durham, A. C., Stewart, K. M., Goss, A. M., Lu, M. M., DeMayo, F. J., & Morrisey, E. E. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44871 · Cited by 164 · see citing works
Kaelin, W. G. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010975 · Cited by 161 · see citing works
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Verma, A., Singh, A., Singh, M. P., Nengroo, M. A., Saini, K. K., Satrusal, S. R., Khan, M. A., Chaturvedi, P., Sinha, A., Meena, S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35059-x · Cited by 148 · see citing works
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Sera, Y., Nakata, Y., Ueda, T., Yamasaki, N., Koide, S., Kobayashi, H., Ikeda, K.-I., Kobatake, K., Iwasaki, M., Oda, H., et al. (2021) · Blood · doi:10.1182/blood.2019001044 · Cited by 42 · see citing works
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van Kempen, L. C. L., Redpath, M., Elchebly, M., Klein, K. O., Papadakis, A. I., Wilmott, J. S., Scolyer, R. A., Edqvist, P.-H., Pontén, F., Schadendorf, D., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aai9188 · Cited by 29 · see citing works
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Thrasher, B. J., Hong, L. K., Whitmire, J. K., & Su, M. A. (2016) · Current Allergy and Asthma Reports · doi:10.1007/s11882-016-0612-y · Cited by 28 · see citing works
- Authors
- van Haaften, G., Dalgliesh, G. L., 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, P. J., Cole, J., Forbes, S., Jia, M., Jones, D., Kok, C. Y., Leroy, C., Lin, M.-L., McBride, D. J., 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, P. S., Turner, R., Turrell, K., Varian, J., West, S., Widaa, S., Wray, P., Collins, V. P., Ichimura, K., Law, S., Wong, J., Yuen, S. T., Leung, S. Y., Tonon, G., DePinho, R. A., Tai, Y.-T., Anderson, K. C., Kahnoski, R. J., Massie, A., Khoo, S. K., Teh, B. T., Stratton, M. R., & Futreal, P. A.
- Affiliations
- Wellcome Sanger Institute (GB)
- University of Cambridge (GB)
- Queen Mary Hospital (CN)
- Harvard University (US)
- Dana-Farber Cancer Institute (US)
- Spectrum Health (US)
- Van Andel Institute (US)
- Institute of Cancer Research (GB)
- Corresponding author
- Stratton, Michael R
- Futreal, P Andrew
- ORCID
- Dalgliesh, Gillian L
- Davies, Helen
- Chen, Lina
- Greenman, Chris
- Edkins, Sarah
- Teague, Jon
- Hinton, Jonathan
- Latimer, Calli
- Barthorpe, Syd
- Buck, Gemma
- Campbell, Peter J
- Jia, Mingming
- Jones, David
- Lin, Meng-Lay
- McBride, David J
- Menzies, Andrew
- Mironenko, Tatiana
- Pleasance, Erin
- Shepherd, Rebecca
- Tarpey, Patrick S
- Widaa, Sara
- Collins, V Peter
- Ichimura, Koichi
- Law, Simon
- Yuen, Siu Tsan
- Tonon, Giovanni
- DePinho, Ronald A
- Tai, Yu-Tzu
- Anderson, Kenneth C
- Kahnoski, Richard J
- Khoo, Sok Kean
- Teh, Bin Tean
- Stratton, Michael R
- Futreal, P Andrew
- Venue
- Nature Genetics
- Published
- 2009-03-29
- Volume
- 41
- Issue
- 5
- Pages
- 521-523
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2873835
- OpenAlex
- W2024985626
- Cited by
- 784
- References
- 16
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 18 · 2023: 32 · 2022: 25 · 2021: 46 · 2020: 42 · 2019: 30 · 2018: 38 · 2017: 45 · 2016: 59 · 2015: 44 · 2014: 72 · 2013: 73 · 2012: 94
- FWCI
- 31.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Wellcome Trust (077012, 088340)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- KDM6A, somatic mutations, tumor suppressor, histone lysine methylation, epigenetic regulation, multiple myeloma, esophageal squamous cell carcinoma, clear cell renal cell carcinoma, myeloid leukemia, breast cancer, colorectal cancer, glioblastoma, gene expression changes
- MeSH terms
- Humans, Mutation, Neoplasms, Oxidoreductases, N-Demethylating, Epigenesis, Genetic, Jumonji Domain-Containing Histone Demethylases
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