Cited by 802Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

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Intragenic ERBB2 kinase mutations in tumours

Stephens, Philip, Hunter, Chris, Bignell, Graham, Edkins, Sarah, Davies, Helen, Teague, Jon, Stevens, Claire, O'Meara, Sarah, Smith, Raffaella, Parker, Adrian, Barthorpe, Andy, Blow, Matthew, Brackenbury, Lisa, Butler, Adam, Clarke, Oliver, Cole, Jennifer, Dicks, Ed, Dike, Angus, Drozd, Anja, Edwards, Ken, Forbes, Simon, Foster, Rebecca, Gray, Kristian, Greenman, Chris, Halliday, Kelly, Hills, Katy, Kosmidou, Vivienne, Lugg, Richard, Menzies, Andy, Perry, Janet, Petty, Robert, Raine, Keiran, Ratford, Lewis, Shepherd, Rebecca, Small, Alexandra, Stephens, Yvonne, Tofts, Calli, Varian, Jennifer, West, Sofie, Widaa, Sara, Yates, Andrew, Brasseur, Francis, Cooper, Colin S., Flanagan, Adrienne M., Knowles, Margaret, Leung, Suet Y., Louis, David N., Looijenga, Leendert H. J., Malkowicz, Bruce, Pierotti, Marco A., Teh, Bin, Chenevix-Trench, Georgia, Weber, Barbara L., Yuen, Siu T., Harris, Grace, Goldstraw, Peter, Nicholson, Andrew G., Futreal, P. Andrew, Wooster, Richard, Stratton, Michael R.·2004·Nature

DOI 10.1038/431525b

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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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Authors: Stephens, P., Hunter, C., Bignell, G., Edkins, S., Davies, H., Teague, J., Stevens, C., O'Meara, S., Smith, R., Parker, A., Barthorpe, A., Blow, M., Brackenbury, L., Butler, A., Clarke, O., Cole, J., Dicks, E., Dike, A., Drozd, A., Edwards, K., Forbes, S., Foster, R., Gray, K., Greenman, C., Halliday, K., Hills, K., Kosmidou, V., Lugg, R., Menzies, A., Perry, J., Petty, R., Raine, K., Ratford, L., Shepherd, R., Small, A., Stephens, Y., Tofts, C., Varian, J., West, S., Widaa, S., Yates, A., Brasseur, F., Cooper, C. S., Flanagan, A. M., Knowles, M., Leung, S. Y., Louis, D. N., Looijenga, L. H. J., Malkowicz, B., Pierotti, M. A., Teh, B., Chenevix-Trench, G., Weber, B. L., Yuen, S. T., Harris, G., Goldstraw, P., Nicholson, A. G., Futreal, P. A., Wooster, R., & Stratton, M. R.
Affiliations: Wellcome Sanger Institute (GB)
Ludwig Cancer Research (BE)
Institute of Cancer Research (GB)
University College London (GB)
Cancer Research UK (GB)
Queen Mary Hospital (CN)
Massachusetts General Hospital (US)
Erasmus MC (NL)
University of Pennsylvania (US)
IFOM (IT)
Van Andel Institute (US)
Royal Brompton Hospital (GB)
Corresponding author: Futreal, P. Andrew
ORCID: Hunter, Chris
Edkins, Sarah
Davies, Helen
Teague, Jon
Blow, Matthew
Clarke, Oliver
Dicks, Ed
Foster, Rebecca
Gray, Kristian
Greenman, Chris
Raine, Keiran
Shepherd, Rebecca
Widaa, Sara
Yates, Andrew
Flanagan, Adrienne M.
Knowles, Margaret
Louis, David N.
Looijenga, Leendert H. J.
Pierotti, Marco A.
Teh, Bin
Yuen, Siu T.
Nicholson, Andrew G.
Futreal, P. Andrew
Stratton, Michael R.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2004-09
Volume: 431
Issue: 7008
Pages: 525-526
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/431525b
OpenAlex: W2049449785
Cited by: 802
References: 7
Citations by year: 2026: 14 · 2025: 25 · 2024: 19 · 2023: 20 · 2022: 31 · 2021: 41 · 2020: 26 · 2019: 26 · 2018: 34 · 2017: 30 · 2016: 20 · 2015: 45 · 2014: 61 · 2013: 46 · 2012: 40
FWCI: 48.46
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
UEA Digital Repository (University of East Anglia) (acceptedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
DIAL (Catholic University of Leuven) (submittedVersion)
Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
UCL Discovery (University College London) (submittedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords: ERBB2, HER2, c-erbB-2, kinase domain mutations, intragenic mutations, lung cancer, lung adenocarcinoma
MeSH terms: Gefitinib, Carcinoma, Non-Small-Cell Lung, DNA Mutational Analysis, Enzyme Activation, Humans, Lung Neoplasms, Models, Molecular, Mutation, Neoplasms, Quinazolines, Protein Structure, Tertiary, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, ErbB Receptors

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