Investigation for tyrosine kinase mutations using novel methods

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Molecular targeted therapies such as crizotinib that target ALK fusion and erlotinib or gefitinib that target EGFR mutations have demonstrated superior single agent activity in selected patients as compared to standard chemotherapy regimes in lung cancer treatment. Recently, a series of new gene fusions have been described in patients with lung cancer associated with the kinase domain of the RET and NTRK1 gene using next generation sequencing. We have developed FISH method to detect RET fusions. In our cohort three RET fusion mutants were found, all were female, non-smoker and adenocarcinomas. Point mutation of the BRAF gene is a genetic event in a subset of lung cancer. In addition, BRAF V600E is a driver mutation that can be effectively targeted with selective BRAF and/or MEK inhibitors. To determine the BRAF mutation status in Japanese lung carcinoma, we investigated BRAF V600E mutations by real time-PCR (CAST-PCR) and immunohistochemical methods using mutation specific antibody.