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A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer

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Abstract

We examined the coding sequence of 518 protein kinases, ∼1.3 Mb of DNA per sample, in 25 breast cancers. In many tumors, we detected no somatic mutations. But a few had numerous somatic mutations with distinctive patterns indicative of either a mutator phenotype or a past exposure.

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Figure 1: Breast cancer mutational spectra.

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Authors and Affiliations

  1. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, Cambridge, UK

    Philip Stephens, Sarah Edkins, Helen Davies, Chris Greenman, Charles Cox, Chris Hunter, Graham Bignell, Jon Teague, Raffaella Smith, Claire Stevens, Sarah O'Meara, Adrian Parker, Patrick Tarpey, Tim Avis, Andy Barthorpe, Lisa Brackenbury, Gemma Buck, Adam Butler, Jody Clements, Jennifer Cole, Ed Dicks, Ken Edwards, Simon Forbes, Matthew Gorton, Kristian Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Jonathon Hinton, David Jones, Vivienne Kosmidou, Ross Laman, Richard Lugg, Andrew Menzies, Janet Perry, Robert Petty, Keiran Raine, Rebecca Shepherd, Alexandra Small, Helen Solomon, Yvonne Stephens, Calli Tofts, Jennifer Varian, Anthony Webb, Sofie West, Sara Widaa, Andrew Yates, Michael R Stratton, P Andrew Futreal & Richard Wooster

  2. Ludwig Institute for Cancer Research, 74 Avenue Hippocrate, Brussels, B-1200, Belgium

    Francis Brasseur

  3. Institute of Cancer Research, Sutton, SM2 5NG, Surrey, UK

    Colin S Cooper & Michael R Stratton

  4. The Institute of Orthopaedics, Univeristy College London, Stanmore, Middlesex, UK

    Adrienne M Flanagan

  5. Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK

    Anthony Green

  6. Cancer Research UK Clinical Centre, St. James University Hospital, Leeds, LS9 7TF, UK

    Maggie Knowles

  7. Department of Pathology, The University of Hong Kong, Hong Kong

    Suet Y Leung & Siu T Yuen

  8. Josephine Nefkens Institute, Erasmus University, Rotterdam, Rotterdam, 3015 GE, The Netherlands

    Leendert H J Looijenga

  9. Division of Urology, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Bruce Malkowicz

  10. Nazionale Tumori and FIRC Institute of Molecular Oncology, Milan, Italy

    Marco A Pierotti

  11. Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, 49503, Michigan, USA

    Bin Teh

  12. Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK

    Andrew G Nicholson

  13. Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, SW3 6JB, UK

    Sunil Lakhani

  14. Cancer Research UK Genetic Epidemiology Group, Strangeways Research Laboratories, Cambridge, CB1 4RN, UK

    Douglas F Easton

  15. University of Pennsylvania Cancer Centre, 421 Curie Boulevard, Philadelphia, 19104, Pennsylvania, USA

    Barbara L Weber

Authors
  1. Philip Stephens
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  2. Sarah Edkins
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  3. Helen Davies
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  4. Chris Greenman
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  5. Charles Cox
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  6. Chris Hunter
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  7. Graham Bignell
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  8. Jon Teague
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  9. Raffaella Smith
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  10. Claire Stevens
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  11. Sarah O'Meara
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  12. Adrian Parker
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  13. Patrick Tarpey
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  14. Tim Avis
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  15. Andy Barthorpe
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  16. Lisa Brackenbury
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  17. Gemma Buck
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  18. Adam Butler
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  19. Jody Clements
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  20. Jennifer Cole
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  21. Ed Dicks
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  22. Ken Edwards
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  23. Simon Forbes
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  24. Matthew Gorton
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  25. Kristian Gray
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  26. Kelly Halliday
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  27. Rachel Harrison
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  28. Katy Hills
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  29. Jonathon Hinton
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  30. David Jones
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  31. Vivienne Kosmidou
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  32. Ross Laman
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  33. Richard Lugg
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  34. Andrew Menzies
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  35. Janet Perry
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  36. Robert Petty
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  37. Keiran Raine
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  38. Rebecca Shepherd
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  39. Alexandra Small
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  40. Helen Solomon
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  41. Yvonne Stephens
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  42. Calli Tofts
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  43. Jennifer Varian
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  44. Anthony Webb
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  45. Sofie West
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  46. Sara Widaa
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  47. Andrew Yates
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  48. Francis Brasseur
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  49. Colin S Cooper
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  50. Adrienne M Flanagan
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  51. Anthony Green
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  52. Maggie Knowles
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  53. Suet Y Leung
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  54. Leendert H J Looijenga
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  55. Bruce Malkowicz
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  56. Marco A Pierotti
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  57. Bin Teh
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  58. Siu T Yuen
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  59. Andrew G Nicholson
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  60. Sunil Lakhani
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  61. Douglas F Easton
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  62. Barbara L Weber
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  63. Michael R Stratton
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  64. P Andrew Futreal
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  65. Richard Wooster
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Corresponding author

Correspondence to Michael R Stratton.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Mutation data for the primary and secondary screen (PDF 47 kb)

Supplementary Table 2

Genes analysed in the primary and secondary screens (XLS 66 kb)

Supplementary Table 3

Samples. (PDF 40 kb)

Supplementary Table 4

Coding strand. (PDF 52 kb)

Supplementary Table 5

Pyrimidine strand. (PDF 51 kb)

Supplementary Methods (PDF 78 kb)

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Stephens, P., Edkins, S., Davies, H. et al. A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer. Nat Genet 37, 590–592 (2005). https://doi.org/10.1038/ng1571

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  • DOI: https://doi.org/10.1038/ng1571

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