Association of Epidermal Growth Factor Receptor (EGFR) Gene Mutations with EGFR Amplification in Advanced Non-small Cell Lung Cancer

Overview

Journal Cancer Sci

Specialty Oncology

Date 2008 Oct 30

PMID 18957054

Citations 18

Authors

Ryotaro Morinaga

Isamu Okamoto

Yoshihiko Fujita

Tokuzo Arao

Masaru Sekijima

Kazuto Nishio

Hiroyuki Ito

Masahiro Fukuoka

Jun-Ichi Kadota

Kazuhiko Nakagawa

Affiliations

Soon will be listed here.

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.

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