A systematic analysis of fractional contributions of various growth signals on the proliferation of lung cancer cells

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Background : Gefitinib is an inhibitor of tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and has recently been introduced in the treatment of advanced lung cancers. Gefitinib is dramatically effective in some patients, whereas it is completely ineffective in others. In addition, gefitinib is known to cause serious drug-induced pneumonitis. Recently, it has been found that the presence of EGFR mutation well corresponds with the effectiveness of gefitinib.Method : Clinical specimens isolated from patients (i.g. specimen, bronchial washing, pleural effusion) contain many normal cells as well as cancer cells. In addition, EGFR shows more than 10 different mutations. These make the identification of EGFR mutations in clinical specimen difficult.Results : We have established a novel detection method for EGFR mutations and named it as PNA-LNA PCR clamp. This method can detect mutations in the presence of 100-fold amount of wild type EGFR. We screened 30 lung cancer cell lines established from Japanese, and found 9 cell lines have mutations. We next investigated 56 clinical specimens (1 biopsy specimen, 16 pleural effusion specimens, 1 needle biopsy specimens, 14 bronchial washing fluid specimens, 5 sputum specimens, 35 paraffin embedded specimens and 3 pericardial effusion specimens). 10 specimens were found to contain cells with EGFR mutations.Discussion : To avoid unnecessary administration of gefinitib to patients, information on EGFR mutation in the clinical specimens gives an invaluable information. PNA-LNA PCR clamp can detect EGFR mutations with a high sensitivity within an hour. PNA-LNA PCR clamp will establish an excellent clinical test beneficial for the diagnosis or treatment of non-small cell lung cancers.