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Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines

Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines
Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines
One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase genetic dependencies in 117 cancer cell lines from ten cancer types. By integrating the siRNA screen data with molecular profiling data, including exome sequencing data, we show how vulnerabilities/genetic dependencies that are associated with mutations in specific cancer driver genes can be identified. By integrating additional data sets into this analysis, including protein-protein interaction data, we also demonstrate that the genetic dependencies associated with many cancer driver genes form dense connections on functional interaction networks. We demonstrate the utility of this resource by using it to predict the drug sensitivity of genetically or histologically defined subsets of tumor cell lines, including an increased sensitivity of osteosarcoma cell lines to FGFR inhibitors and SMAD4 mutant tumor cells to mitotic inhibitors.
2211-1247
2490-2501
Campbell, J
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Ryan, CJ
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Brough, R
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Bajrami, I
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Pemberton, HN
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Chong, IY
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Costa-Cabral, S
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Frankum, J
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Gulati, A
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Holme, H
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Miller, R
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Postel-Vinay, S
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Rafiq, R
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Wei, W
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Williamson, CT
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Quigley, DA
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Tym, J
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Al-Lazikani, B
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Fenton, TR
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Natrajan, R
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Strauss, SJ
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Ashworth, A
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Lord, CJ
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Campbell, J
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Ryan, CJ
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Brough, R
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Bajrami, I
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Pemberton, HN
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Chong, IY
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Costa-Cabral, S
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Frankum, J
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Gulati, A
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Holme, H
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Miller, R
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Postel-Vinay, S
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Rafiq, R
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Wei, W
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Williamson, CT
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Quigley, DA
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Tym, J
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Al-Lazikani, B
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Fenton, TR
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Natrajan, R
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Strauss, SJ
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Ashworth, A
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Lord, CJ
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Campbell, J, Ryan, CJ, Brough, R, Bajrami, I, Pemberton, HN, Chong, IY, Costa-Cabral, S, Frankum, J, Gulati, A, Holme, H, Miller, R, Postel-Vinay, S, Rafiq, R, Wei, W, Williamson, CT, Quigley, DA, Tym, J, Al-Lazikani, B, Fenton, TR, Natrajan, R, Strauss, SJ, Ashworth, A and Lord, CJ (2016) Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines. Cell Reports, 14 (10), 2490-2501. (doi:10.1016/j.celrep.2016.02.023).

Record type: Article

Abstract

One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase genetic dependencies in 117 cancer cell lines from ten cancer types. By integrating the siRNA screen data with molecular profiling data, including exome sequencing data, we show how vulnerabilities/genetic dependencies that are associated with mutations in specific cancer driver genes can be identified. By integrating additional data sets into this analysis, including protein-protein interaction data, we also demonstrate that the genetic dependencies associated with many cancer driver genes form dense connections on functional interaction networks. We demonstrate the utility of this resource by using it to predict the drug sensitivity of genetically or histologically defined subsets of tumor cell lines, including an increased sensitivity of osteosarcoma cell lines to FGFR inhibitors and SMAD4 mutant tumor cells to mitotic inhibitors.

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Published date: 1 March 2016
Additional Information: This is an open access article under the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/).

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Local EPrints ID: 453903
URI: http://eprints.soton.ac.uk/id/eprint/453903
ISSN: 2211-1247
PURE UUID: fb16c8f5-da62-4851-8506-0df29e434539
ORCID for TR Fenton: ORCID iD orcid.org/0000-0002-4737-8233

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Date deposited: 25 Jan 2022 17:50
Last modified: 17 Mar 2024 04:11

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Contributors

Author: J Campbell
Author: CJ Ryan
Author: R Brough
Author: I Bajrami
Author: HN Pemberton
Author: IY Chong
Author: S Costa-Cabral
Author: J Frankum
Author: A Gulati
Author: H Holme
Author: R Miller
Author: S Postel-Vinay
Author: R Rafiq
Author: W Wei
Author: CT Williamson
Author: DA Quigley
Author: J Tym
Author: B Al-Lazikani
Author: TR Fenton ORCID iD
Author: R Natrajan
Author: SJ Strauss
Author: A Ashworth
Author: CJ Lord

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