Systematic identification of genomic markers of drug sensitivity in cancer cells (original) (raw)

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Acknowledgements

We thank P. Lo Grasso of the Scripps Research Institute for providing the inhibitor JNK9L. This work was supported by a grant from the Wellcome Trust (086357; M.R.S., P.A.F., J.S., D.A.H.) and by grants from the National Institutes of Health (P41GM079575-02 to N.S.G. and 1U54HG006097-01 to N.S.G. and D.A.H.). S.R. is supported by a Physician-Scientist Early Career Award from the Howard Hughes Medical Institute. U.M. is supported by a Cancer Research UK Clinician Scientist Fellowship.

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Author notes

1. Chris D. Greenman & Sreenath V. Sharma
   Present address: Present addresses: Department of Computing, University of East Anglia, Norwich NR4 7TJ, UK (C.D.G.); The Genome Analysis Centre, Norwich Research Park, Norwich NR4 7UH, UK (C.D.G.); Oncology Drug Discovery, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA (S.V.S.).,
2. Mathew J. Garnett, Elena J. Edelman and Sonja J. Heidorn: These authors contributed equally to this work.

Authors and Affiliations

1. Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK,
   Mathew J. Garnett, Sonja J. Heidorn, Chris D. Greenman, King Wai Lau, I. Richard Thompson, Jorge Soares, Francesco Iorio, Graham R. Bignell, Helen Davies, Syd Barthorpe, Fiona Kogera, Karl Lawrence, Anne McLaren-Douglas, Tatiana Mironenko, Laura Richardson, Frances Jewitt, Patrick O’Brien, Stacey Price, Wanjuan Yang, Adam Butler, P. Andrew Futreal, Michael R. Stratton & Ultan McDermott
2. Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, 02129, Massachusetts, USA
   Elena J. Edelman, Anahita Dastur, Patricia Greninger, Xi Luo, Li Chen, Randy J. Milano, Ah T. Tam, Jesse A. Stevenson, Stephen R. Lutz, Xeni Mitropoulos, Helen Thi, Jessica L. Boisvert, Jose Baselga, Jeffrey A. Engelman, Sreenath V. Sharma, Jeffrey Settleman, Daniel A. Haber, Sridhar Ramaswamy & Cyril H. Benes
3. Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston Massachusetts 02115, USA,
   Qingsong Liu, Wenjun Zhou, Tinghu Zhang, Wooyoung Hur, Xianming Deng, Hwan Geun Choi, Jae Won Chang & Nathanael S. Gray
4. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA,
   Qingsong Liu, Wenjun Zhou, Tinghu Zhang, Wooyoung Hur, Xianming Deng, Hwan Geun Choi, Jae Won Chang & Nathanael S. Gray
5. EMBL-EBI, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK,
   Francesco Iorio & Julio Saez-Rodriguez
6. Laboratoire de génétique et biologie des cancers, Institut Curie, 75248 Paris, Cedex 05, France,
   Didier Surdez & Olivier Delattre
7. Division of Experimental Pathology, Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), 1005 Lausanne, Switzerland,
   Ivan Stamenkovic
8. Howard Hughes Medical Institute, Chevy Chase, 20815, Maryland, USA
   Daniel A. Haber

Authors

1. Mathew J. Garnett
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2. Elena J. Edelman
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3. Sonja J. Heidorn
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4. Chris D. Greenman
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5. Anahita Dastur
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6. King Wai Lau
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7. Patricia Greninger
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8. I. Richard Thompson
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9. Xi Luo
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10. Jorge Soares
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11. Qingsong Liu
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12. Francesco Iorio
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13. Didier Surdez
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14. Li Chen
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15. Randy J. Milano
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16. Graham R. Bignell
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17. Ah T. Tam
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18. Helen Davies
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19. Jesse A. Stevenson
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20. Syd Barthorpe
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21. Stephen R. Lutz
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22. Fiona Kogera
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23. Karl Lawrence
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24. Anne McLaren-Douglas
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25. Xeni Mitropoulos
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26. Tatiana Mironenko
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27. Helen Thi
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28. Laura Richardson
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29. Wenjun Zhou
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30. Frances Jewitt
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31. Tinghu Zhang
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32. Patrick O’Brien
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33. Jessica L. Boisvert
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34. Stacey Price
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35. Wooyoung Hur
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36. Wanjuan Yang
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37. Xianming Deng
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38. Adam Butler
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39. Hwan Geun Choi
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40. Jae Won Chang
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41. Jose Baselga
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42. Ivan Stamenkovic
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43. Jeffrey A. Engelman
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44. Sreenath V. Sharma
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45. Olivier Delattre
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46. Julio Saez-Rodriguez
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47. Nathanael S. Gray
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48. Jeffrey Settleman
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49. P. Andrew Futreal
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50. Daniel A. Haber
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51. Michael R. Stratton
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52. Sridhar Ramaswamy
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53. Ultan McDermott
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54. Cyril H. Benes
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Contributions

M.J.G., C.H.B., U.M. and S.V.S. supervised data collection. M.J.G., C.H.B., U.M. and S.R. supervised data analysis. C.D.G. and K.W.L. conceived and wrote the curve-fitting algorithm and performed the MANOVA; E.J.E. and S.R. performed elastic net analysis and analysed the data. P.G., I.R.T. and J.So. developed and managed screening databases with assistance from A.B. and W.Y.; S.J.H. performed most of the Ewing’s sarcoma related studies with contributions from D.S., A.D., X.L., F.K. and L.C., with I.S. and O.D. providing critical reagents; R.J.M., A.T.T., J.A.S., S.B., S.R.L., K.L., A.M.-D., J.L.B., X.M., T.M., H.T., L.R., F.J. and P.O’B. performed cell line screening experiments. S.P. performed MCL1 siRNA experiments. Q.L.,W.Z., T.Z., W.H., X.D., H.G.C. and J.W.C. synthesized screening compounds, and N.S.G. provided guidance on their selection and use; F.I. and J.S.-R. performed compound activity clustering; G.R.B. and H.D. performed cell line genotyping and genetic analysis; J.A.E. and J.B. provided guidance regarding clinical relevance of the work; M.J.G. and C.H.B. wrote the manuscript with major contributions from S.R., S.J.H. and U.M.; M.R.S., D.A.H., J.Se. and P.A.F. conceived the study, analysed the data and edited the manuscript.

Corresponding authors

Correspondence toUltan McDermott or Cyril H. Benes.

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Competing interests

J.Se. is currently an employee of Genentech and is a shareholder of Roche.

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Garnett, M., Edelman, E., Heidorn, S. et al. Systematic identification of genomic markers of drug sensitivity in cancer cells.Nature 483, 570–575 (2012). https://doi.org/10.1038/nature11005

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• Received: 25 July 2011
• Accepted: 02 March 2012
• Published: 28 March 2012
• Issue Date: 29 March 2012
• DOI: https://doi.org/10.1038/nature11005