Lung cancer: intragenic ERBB2 kinase mutations in tumours

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 EdwardsSimon Forbes, Rebecca Foster, Kristian Gray, Christopher 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, Francis Brasseur, Colin S. Cooper, Adrienne M. Flanagan, Margaret Knowles, Suet Y. Leung, David N. Louis, Leendert H. J. Looijenga, Bruce Malkowicz, Marco A. Pierotti, Bin Teh, Georgia Chenevix-trench, Barbara L. Weber, Siu T. Yuen, Grace Harris, Peter Goldstraw, Andrew G. Nicholson, P. Andrew Futreal, Richard Wooster, Michael R. Stratton

Research output: Contribution to journalArticlepeer-review

618 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)525-526
Number of pages2
JournalNature
Volume431
Issue number7008
DOIs
Publication statusPublished - 30 Sep 2004

Keywords

  • Carcinoma, Non-Small-Cell Lung
  • DNA Mutational Analysis
  • Enzyme Activation
  • Humans
  • Lung Neoplasms
  • Models, Molecular
  • Mutation
  • Neoplasms
  • Protein Structure, Tertiary
  • Quinazolines
  • Receptor, Epidermal Growth Factor
  • Receptor, erbB-2

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