title: Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines.
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.
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: James
authors.initials: J
authors.lastname: Campbell
authors.affiliation: Systems Biology Ireland, University College Dublin, Dublin 4, Ireland.
authors.forename: Colm J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Brough
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Ilirjana
authors.initials: I
authors.lastname: Bajrami
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Helen N
authors.initials: HN
authors.lastname: Pemberton
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK; Royal Marsden Hospital, London SW3 6JJ, UK.
authors.forename: Irene Y
authors.initials: IY
authors.lastname: Chong
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Costa-Cabral
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Frankum
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Aditi
authors.initials: A
authors.lastname: Gulati
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK; UCL Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Harriet
authors.initials: H
authors.lastname: Holme
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK; UCL Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Rowan
authors.initials: R
authors.lastname: Miller
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK; Gustave Roussy Cancer Campus, 94805 Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Postel-Vinay
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Rumana
authors.initials: R
authors.lastname: Rafiq
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wei
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Chris T
authors.initials: CT
authors.lastname: Williamson
authors.affiliation: UCSF Helen Diller Family Comprehensive Cancer Centre, San Francisco, CA 94158, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Quigley
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton SM2 5NG, UK.
authors.forename: Joe
authors.initials: J
authors.lastname: Tym
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton SM2 5NG, UK.
authors.forename: Bissan
authors.initials: B
authors.lastname: Al-Lazikani
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Fenton
authors.affiliation: Functional Genomics Laboratory, The Breast Cancer Now Research Centre, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Rachael
authors.initials: R
authors.lastname: Natrajan
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Strauss
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK. Electronic address: alan.ashworth@ucsf.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.affiliation: The Breast Cancer Now Research Centre and CRUK Gene Function Laboratory, The Institute of Cancer Research, London SW3 6JB, UK. Electronic address: chris.lord@icr.ac.uk.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lord
mesh_terms: D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D011494:Protein Kinases; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051901:Smad4 Protein; C508053:ERBB2 protein, human