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Lung cancer

Intragenic ERBB2 kinase mutations in tumours

Nature volume 431, pages 525–526 (2004)Cite this article

Abstract

The protein-kinase family is the most frequently mutated gene family found in human cancer and faulty kinase enzymes are being investigated as promising targets for the design of antitumour therapies. We have sequenced the gene encoding the transmembrane protein tyrosine kinase ERBB2 (also known as HER2 or Neu) from 120 primary lung tumours and identified 4% that have mutations within the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had mutations. ERBB2 inhibitors, which have so far proved to be ineffective in treating lung cancer, should now be clinically re-evaluated in the specific subset of patients with lung cancer whose tumours carry ERBB2 mutations.

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Figure 1: Similar positioning within the epidermal growth-factor receptor (EGFR) kinase domain (database accession numbers MMDB:20494/PDB:1M17) of the EGFR and ERBB2 mutations that are found in a proportion of lung tumours.

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Authors and Affiliations

  1. Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK

    Philip Stephens, Chris Hunter, Graham Bignell, Sarah Edkins, Helen Davies, Jon Teague, Claire Stevens, Sarah O'Meara, Raffaella Smith, Adrian Parker, Andy Barthorpe, Matthew Blow, Lisa Brackenbury, Adam Butler, Oliver Clarke, Jennifer Cole, Ed Dicks, Angus Dike, Anja Drozd, Ken Edwards, Simon Forbes, Rebecca Foster, Kristian Gray, Chris Greenman, Kelly Halliday, Katy Hills, Vivienne Kosmidou, Richard Lugg, Andy Menzies, Janet Perry, Robert Petty, Keiran Raine, Lewis Ratford, Rebecca Shepherd, Alexandra Small, Yvonne Stephens, Calli Tofts, Jennifer Varian, Sofie West, Sara Widaa, Andrew Yates, P. Andrew Futreal, Richard Wooster & Michael R. Stratton

  2. Ludwig Institute for Cancer Research, Brussels, 1200, Belgium

    Francis Brasseur

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

    Colin S. Cooper & Michael R. Stratton

  4. Institute of Orthopaedics, University College London, Stanmore, HA7 4LP, UK

    Adrienne M. Flanagan

  5. Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, LS9 7TF, UK

    Margaret Knowles

  6. University of Hong Kong Department of Pathology, Queen Mary Hospital, Hong Kong

    Suet Y. Leung & Siu T. Yuen

  7. Massachusetts General Hospital East, Molecular Pathology Unit, Charlestown, 02129, Massachusetts, USA

    David N. Louis

  8. Laboratory of Pathology/Experimental Patho-Oncology, Erasmus MC University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Josephine Nefkens Institute, Rotterdam, 3000 DR, The Netherlands

    Leendert H. J. Looijenga

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

    Bruce Malkowicz

  10. Instituto 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. Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, 4029, Queensland, Australia

    Georgia Chenevix-Trench

  13. University of Pennsylvania Cancer Centre, Philadelphia, 19104-6160, Pennsylvania, USA

    Barbara L. Weber

  14. Royal Brompton Hospital, London, SW3 6NP, UK

    Grace Harris, Peter Goldstraw & Andrew G. Nicholson

  15. Cancer Genome Project and Collaborative Group,

    Philip Stephens

Authors
  1. Philip Stephens
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  2. Chris Hunter
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  3. Graham Bignell
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  9. Raffaella Smith
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  10. Adrian Parker
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  14. Adam Butler
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  15. Oliver Clarke
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  16. Jennifer Cole
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  19. Anja Drozd
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  20. Ken Edwards
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  21. Simon Forbes
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  22. Rebecca Foster
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  23. Kristian Gray
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  24. Chris Greenman
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  25. Kelly Halliday
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  26. Katy Hills
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  27. Vivienne Kosmidou
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  28. Richard Lugg
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  34. Rebecca Shepherd
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  35. Alexandra Small
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  36. Yvonne Stephens
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  38. Jennifer Varian
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  39. Sofie West
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  40. Sara Widaa
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  41. Andrew Yates
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  42. Francis Brasseur
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  43. Colin S. Cooper
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  44. Adrienne M. Flanagan
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  45. Margaret Knowles
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  46. Suet Y. Leung
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  47. David N. Louis
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  48. Leendert H. J. Looijenga
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  49. Bruce Malkowicz
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  50. Marco A. Pierotti
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  51. Bin Teh
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  52. Georgia Chenevix-Trench
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  53. Barbara L. Weber
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  54. Siu T. Yuen
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  55. Grace Harris
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  56. Peter Goldstraw
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  57. Andrew G. Nicholson
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  58. P. Andrew Futreal
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  59. Richard Wooster
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  60. Michael R. Stratton
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Corresponding author

Correspondence to P. Andrew Futreal.

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The authors declare no competing financial interests.

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Stephens, P., Hunter, C., Bignell, G. et al. Intragenic ERBB2 kinase mutations in tumours. Nature 431, 525–526 (2004). https://doi.org/10.1038/431525b

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