Open AccessAssociation of epidermal growth factor receptor ( EGFR ) gene mutations with EGFR amplification in advanced non‐small cell lung cancer
Author(s) -
Morinaga Ryotaro,
Okamoto Isamu,
Fujita Yoshihiko,
Arao Tokuzo,
Sekijima Masaru,
Nishio Kazuto,
Ito Hiroyuki,
Fukuoka Masahiro,
Kadota Junichi,
Nakagawa Kazuhiko
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00962.x
Subject(s) - polysomy , epidermal growth factor receptor , lung cancer , gefitinib , cancer research , biology , fluorescence in situ hybridization , copy number variation , mutation , erlotinib , egfr inhibitors , gene duplication , tyrosine kinase inhibitor , somatic cell , cancer , oncology , medicine , gene , genetics , genome , chromosome
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. ( Cancer Sci 2008; 99: 2455–2460)