Investigation for tyrosine kinase mutations using novel methods

分子靶向治疗（如靶向ALK融合的克唑替尼和靶向EGFR突变的厄洛替尼或吉非替尼）在选定患者中的单药活性优于肺癌治疗中的标准化疗方案。最近，一系列新的基因融合已被描述在肺癌患者与RET和NTRK 1基因的激酶结构域使用下一代测序。我们已经开发了FISH方法来检测RET融合。在我们的队列中发现了三个RET融合突变体，均为女性、非吸烟者和腺癌。BRAF基因的点突变是肺癌的一个亚类的遗传事件。此外，BRAF V600 E是一种驱动突变，可以用选择性BRAF和/或MEK抑制剂有效靶向。为了确定日本肺癌中BRAF突变状态，我们采用真实的时间PCR（CAST-PCR）和免疫组织化学方法，使用突变特异性抗体研究BRAF V600 E突变。

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.