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The activating mutations of the kinase domain of the epidermal growth factor receptor (EGFR) gene are frequently found in a subset of non-small-cell lung cancers (NSCLC). The frequency of mutations of EGFR gene is 30~40 percent and higher in especially Japanese female patients with adenocarcinoma. Most mutations were small deletions in exon 19 and R858L point mutation in exon 21. Several studies showed that microsatellite alterations and gene mutations were detected in the serum DNA of patients with early stage lung cancer as well as advanced lung cancer. The EGFR gene mutation might be good candidate biomarker for the early detection of the lung cancer, especially adenocarcinoma using the sensitive methods because of the high frequency and few types of the EGFR mutations. EGFR mutations in serum DNA of advanced NSCLC patients were detected by sensitive assay for the EGFR mutations and correlated with the effect of EGFR inhibitors (Kimura et al. Clin Cancer Res. 2006). However, the EGFR mutations in serum DNA of patients with early stage lung cancer were not examined yet. In this study, we examined whether the mutations of the EGFR genes could be detected in the serum of surgically resected NSCLC patients. Mutation analysis of EGFR gene in primary tumor specimens showed that 13 patients had small deletions of exon 19 and 21 patients had 858 mutations in exon 21. The serum of 34 patients with EGFR-mutated tumor were obtained at the time of operations and stored at - 80°C. Nagai et al. developed the peptide nuclei acid-locker nucleic acid polymerase chain reaction clamp (PNA-LNA PCR clamp) as sensitive assay for the detection of the EGFR mutation (Cancer Res 2004). DNA was purified from serum and the EGFR mutation was examined by this method (Mitsubishi Chemical Medience Corporation, Tokyo, Japan). We found EGFR mutation (deletion in exon 19) identical to primary tumor in the serum DNA of one patient out of 34 EGFR-mutated patients. The patient developed brain metastasis three years after surgery. The result showed that the detection of the EGFR mutation in the serum of resected lung cancer patients, is not frequent suggesting that the amount of circulating DNA derived from lung cancers of early stage patients were very small.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA