Investigation for tyrosine kinase mutations using novel methods

使用新方法研究酪氨酸激酶突变

• 批准号: 23659674
• 负责人: FUJII Yoshitaka
• 金额: $ 2.66万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659674/
• 关键词: EGFR; RET; NTRK1; BRAF; CAST-PCR; Immunohistochemistry; V600E; NTRK; NRF2; KIF5B/RET; 肺癌; FISH; CISH

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.

分子靶向疗法，如靶向ALK融合的克里唑替尼和靶向EGFR突变的厄洛替尼或吉非替尼，与肺癌治疗的标准化疗方案相比，在选定的患者中显示出优越的单药活性。最近，利用下一代测序技术，在肺癌患者中发现了一系列与RET和NTRK1基因激酶结构域相关的新基因融合。我们开发了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基因点突变是肺癌亚群中的一种遗传事件。此外，BRAF V600E是一种驱动突变，可通过选择性BRAF和/或MEK抑制剂有效靶向。为了确定BRAF在日本肺癌中的突变状态，我们采用real - time-PCR （CAST-PCR）和突变特异性抗体免疫组化方法检测BRAF V600E突变。

项目成果

Increased NRF2 gene (NFE2L2) copy number correlates with mutations in lung squamous cell carcinomas

NRF2 基因 (NFE2L2) 拷贝数增加与肺鳞状细胞癌突变相关

• DOI: 10.3892/mmr.2012.921
• 发表时间: 2012
• 期刊: Mol Med Rep
• 影响因子: 3.4
• 作者: Sasaki H;Shitara M;Yokota K;Hikosaka Y;Moriyama S;Yano M;Fujii Y.
• 通讯作者: Fujii Y.

KIF5B/RET fusion gene in surgically-treated Japanese adenocarcinoma of the lung

手术治疗的日本肺腺癌中的 KIF5B/RET 融合基因

• 发表时间: 2013
• 作者: Sasaki H;Shimizu S;Tani Y;Okuda K;Hikosaka Y;Moriyama S;Yano M;Fujii Y
• 通讯作者: Fujii Y

肺癌患者におけるNRF2遺伝子コピー数の検討

肺癌患者NRF2基因拷贝数检测

• 发表时间: 2012
• 作者: 佐々木秀文;設楽将之;奥田勝裕;彦坂雄;森山悟;矢野智紀;藤井義敬
• 通讯作者: 藤井義敬

外科的切除を行った肺腺癌におけるLKB1遺伝子変異についての検討

手术切除肺腺癌中 LKB1 基因突变的检查

• 发表时间: 2012
• 作者: 奥田勝裕;佐々木秀文;矢野智紀;森山悟;彦坂雄;横田圭右;設楽将之;藤井義敬
• 通讯作者: 藤井義敬

日本人肺癌症例におけるRET発現とKIF5B/RET遺伝子転座の同定法

日本肺癌病例中 RET 表达和 KIF5B/RET 基因易位的鉴定方法

• 发表时间: 2012
• 作者: 奥田勝裕;佐々木秀文;矢野智紀;森山悟;彦坂雄;藤井義敬
• 通讯作者: 藤井義敬