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

658 Citations (Scopus)

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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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

Van Haaften, Gijs ; Dalgliesh, Gillian L ; Davies, Helen ; Chen, Lina ; Bignell, Graham ; Greenman, Christopher ; 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. / Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. In: Nature Genetics. 2009 ; Vol. 41, No. 5. pp. 521-523.

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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.",

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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

Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. / Van Haaften, Gijs; Dalgliesh, Gillian L; Davies, Helen; Chen, Lina; Bignell, Graham; Greenman, Christopher; 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.

In: Nature Genetics, Vol. 41, No. 5, 01.05.2009, p. 521-523.

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

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AU - Davies, Helen

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AU - Hardy, Claire

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AU - Beare, Dave

AU - Buck, Gemma

AU - Campbell, Peter J

AU - Cole, Jennifer

AU - Forbes, Simon

AU - Jia, Mingming

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AU - Leroy, Catherine

AU - Lin, Meng-lay

AU - Mcbride, David J

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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 - Varian, Jennifer

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AU - Widaa, Sara

AU - Wray, Paul

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AU - Ichimura, Koichi

AU - Law, Simon

AU - Wong, John

AU - Yuen, Siu Tsan

AU - Leung, Suet Yi

AU - Tonon, Giovanni

AU - Depinho, Ronald A

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AU - Anderson, Kenneth C

AU - Kahnoski, Richard J

AU - Massie, Aaron

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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.

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