Association of epidermal growth factor receptor (EGFR) gene mutations with EGFR amplification in advanced non-small cell lung cancer

Ryotaro Morinaga, Isamu Okamoto, Yoshihiko Fujita, Tokuzo Arao, Masaru Sekijima, Kazuto Nishio, Hiroyuki Ito, Masahiro Fukuoka, Jun Ichi Kadota, Kazuhiko Nakagawa

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30 Citations (Scopus)

Abstract

Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with the response to EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Increased EGFR copy number has also been associated with sensitivity to these drugs. However, given that it is often difficult to obtain sufficient amounts of tumor tissue for genetic analysis from patients with advanced NSCLC, the relationship between these two types of EGFR alterations has remained unclear. We have now evaluated EGFR mutation status both by direct sequencing and with a high-sensitivity assay, the Scorpion-amplification-refractory mutation system, and have determined EGFR copy number by fluorescence in.situ hybridization (FISH) analysis in paired tumor specimens obtained from 100 consecutive patients with advanced NSCLC treated with chemotherapy. EGFR mutations or FISH positivity (EGFR amplification or high polysomy) were apparent in 18% (18/100) and 32% (32/100) of patients, respectively. The Scorpion-amplification-refractory mutation system was more sensitive than direct sequencing for the detection of EGFR mutations. Furthermore, EGFR mutations were associated with EGFR amplification (P = 0.009) but not with FISH positivity (P = 0.266). Our results therefore suggest the existence of a significant association between EGFR mutation and EGFR amplification in patients with advanced NSCLC.

Original languageEnglish
Pages (from-to)2455-2460
Number of pages6
JournalCancer Science
Volume99
Issue number12
DOIs
Publication statusPublished - Dec 12 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Morinaga, R., Okamoto, I., Fujita, Y., Arao, T., Sekijima, M., Nishio, K., Ito, H., Fukuoka, M., Kadota, J. I., & Nakagawa, K. (2008). Association of epidermal growth factor receptor (EGFR) gene mutations with EGFR amplification in advanced non-small cell lung cancer. Cancer Science, 99(12), 2455-2460. https://doi.org/10.1111/j.1349-7006.2008.00962.x