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

Gijs Van Haaften; Gillian L Dalgliesh; Helen Davies; Lina Chen; Graham Bignell; Christopher Greenman; Sarah Edkins; Claire Hardy; Sarah O'meara; Jon Teague; Adam Butler; Jonathan Hinton; Calli Latimer; Jenny Andrews; Syd Barthorpe; Dave Beare; Gemma Buck; Peter J Campbell; Jennifer Cole; Simon Forbes; Mingming Jia; David Jones; Chai Yin Kok; Catherine Leroy; Meng-lay Lin; David J Mcbride; Mark Maddison; Simon Maquire; Kirsten Mclay; Andrew Menzies; Tatiana Mironenko; Lee Mulderrig; Laura Mudie; Erin Pleasance; Rebecca Shepherd; Raffaella Smith; Lucy Stebbings; Philip Stephens; Gurpreet Tang; Patrick S Tarpey; Rachel Turner; Kelly Turrell; Jennifer Varian; Sofie West; Sara Widaa; Paul Wray; V Peter Collins; Koichi Ichimura; Simon Law; John Wong; Siu Tsan Yuen; Suet Yi Leung; Giovanni Tonon; Ronald A Depinho; Yu-tzu Tai; Kenneth C Anderson; Richard J Kahnoski; Aaron Massie; Sok Kean Khoo; Bin Tean Teh; Michael R Stratton; P Andrew Futreal

doi:10.1038/ng.349

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

Gijs Van Haaften, Gillian L Dalgliesh, Helen Davies, Lina Chen, Graham Bignell, Christopher Greenman, Sarah Edkins, Claire Hardy, Sarah O'meara, Jon Teague, Adam Butler, Jonathan Hinton, Calli Latimer, Jenny Andrews, Syd Barthorpe, Dave Beare, Gemma Buck, Peter J Campbell, Jennifer Cole, Simon ForbesMingming Jia, David Jones, Chai Yin Kok, Catherine Leroy, Meng-lay Lin, David J Mcbride, Mark Maddison, Simon Maquire, Kirsten Mclay, Andrew Menzies, Tatiana Mironenko, Lee Mulderrig, Laura Mudie, Erin Pleasance, Rebecca Shepherd, Raffaella Smith, Lucy Stebbings, Philip Stephens, Gurpreet Tang, Patrick S Tarpey, Rachel Turner, Kelly Turrell, Jennifer Varian, Sofie West, Sara Widaa, Paul Wray, V Peter Collins, Koichi Ichimura, Simon Law, John Wong, Siu Tsan Yuen, Suet Yi Leung, Giovanni Tonon, Ronald A Depinho, Yu-tzu Tai, Kenneth C Anderson, Richard J Kahnoski, Aaron Massie, Sok Kean Khoo, Bin Tean Teh, Michael R Stratton, P Andrew Futreal

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	521-523
Number of pages	3
Journal	Nature Genetics
Volume	41
Issue number	5
DOIs	https://doi.org/10.1038/ng.349
Publication status	Published - 1 May 2009

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Cite this

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., ... Futreal, P. A. (2009). Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nature Genetics, 41(5), 521-523. https://doi.org/10.1038/ng.349

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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.",

author = "{Van Haaften}, Gijs and Dalgliesh, {Gillian L} and Helen Davies and Lina Chen and Graham Bignell and Christopher Greenman and Sarah Edkins and Claire Hardy and Sarah O'meara and Jon Teague and Adam Butler and Jonathan Hinton and Calli Latimer and Jenny Andrews and Syd Barthorpe and Dave Beare and Gemma Buck and Campbell, {Peter J} and Jennifer Cole and Simon Forbes and Mingming Jia and David Jones and Kok, {Chai Yin} and Catherine Leroy and Meng-lay Lin and Mcbride, {David J} and Mark Maddison and Simon Maquire and Kirsten Mclay and Andrew Menzies and Tatiana Mironenko and Lee Mulderrig and Laura Mudie and Erin Pleasance and Rebecca Shepherd and Raffaella Smith and Lucy Stebbings and Philip Stephens and Gurpreet Tang and Tarpey, {Patrick S} and Rachel Turner and Kelly Turrell and Jennifer Varian and Sofie West and Sara Widaa and Paul Wray and Collins, {V Peter} and Koichi Ichimura and Simon Law and John Wong and Yuen, {Siu Tsan} and Leung, {Suet Yi} and Giovanni Tonon and Depinho, {Ronald A} and Yu-tzu Tai and Anderson, {Kenneth C} and Kahnoski, {Richard J} and Aaron Massie and Khoo, {Sok Kean} and Teh, {Bin Tean} and Stratton, {Michael R} and Futreal, {P Andrew}",

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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, M, 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, Y, Anderson, KC, Kahnoski, RJ, Massie, A, Khoo, SK, Teh, BT, Stratton, MR & Futreal, PA 2009, 'Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer', Nature Genetics, vol. 41, no. 5, pp. 521-523. https://doi.org/10.1038/ng.349

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AU - Dalgliesh, Gillian L

AU - Davies, Helen

AU - Chen, Lina

AU - Bignell, Graham

AU - Greenman, Christopher

AU - Edkins, Sarah

AU - Hardy, Claire

AU - O'meara, Sarah

AU - Teague, Jon

AU - Butler, Adam

AU - Hinton, Jonathan

AU - Latimer, Calli

AU - Andrews, Jenny

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AU - Buck, Gemma

AU - Campbell, Peter J

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AU - Forbes, Simon

AU - Jia, Mingming

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AU - Kok, Chai Yin

AU - Leroy, Catherine

AU - Lin, Meng-lay

AU - Mcbride, David J

AU - Maddison, Mark

AU - Maquire, Simon

AU - Mclay, Kirsten

AU - Menzies, Andrew

AU - Mironenko, Tatiana

AU - Mulderrig, Lee

AU - Mudie, Laura

AU - Pleasance, Erin

AU - Shepherd, Rebecca

AU - Smith, Raffaella

AU - Stebbings, Lucy

AU - Stephens, Philip

AU - Tang, Gurpreet

AU - Tarpey, Patrick S

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AU - Tonon, Giovanni

AU - Depinho, Ronald A

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AU - Anderson, Kenneth C

AU - Kahnoski, Richard J

AU - Massie, Aaron

AU - Khoo, Sok Kean

AU - Teh, Bin Tean

AU - Stratton, Michael R

AU - Futreal, P Andrew

PY - 2009/5/1

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N2 - 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.

AB - 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.

U2 - 10.1038/ng.349

DO - 10.1038/ng.349

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