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Analysis and identify of gene associated with EGFR mutation by gene chip for SNPs

SNPs基因芯片分析鉴定EGFR突变相关基因

基本信息

批准号：
21591012
负责人：
MAEMONDO Makoto
金额：
$ 2.91万
依托单位：
地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所) (2011)Miyagi Cancer Center Research Institute (2009-2010)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591012/
关键词：
非小細胞肺癌 EGFR遺伝子変異全ゲノムSNP解析癌遺伝子

项目摘要

Lung cancer is a major cause of cancer death, and one of the most resistant cancers to treatment. Several mutations in the lung tumor were found in female, non-smoker patients with adenocarcinoma. These mutations were associated with not only oncogenicity but the target of therapy. Gefitinib is an orally administered tyrosine kinase inhibitor(TKI) of EGFR that was approved in Japan for the first time in the world. This drug has substantial role on treatment with non-small cell lung cancer patients who have characteristics that include female, never smoker, and adenocarcinoma histology. The response of treatment with gefitinib was found strongly correlated with both these patient characteristics and EGFR mutations. In addition, it was reported that there are more frequent EGFR mutations in Asian patients than in Westerners. On the hypothesis of that there are some genes associated with this ethnic difference in incidence of mutation, we conducted the study to identify these associated genes by the analysis of SNP through the whole genome with Gene chip assay.Result : We collected blood samples from 64 patients with EGFR mutation and extracted DNA and analyzed whole genome SNP with SNP Array 6.0 which defined SNPs in more than 900, 000 sites. We found two sites associated with EGFR activating mutation with this method. We are planning to conduct re-examination with other sample set.

肺癌是癌症死亡的主要原因之一，也是最难治疗的癌症之一。在女性非吸烟腺癌患者中发现了一些肺肿瘤突变。这些突变不仅与致癌性有关，而且与治疗目标有关。吉非替尼（Gefitinib）是一种口服的EGFR酪氨酸激酶抑制剂（TKI），在全球首次在日本获批。该药物在治疗非小细胞肺癌患者中具有重要作用，这些患者具有包括女性，从不吸烟和腺癌组织学的特征。发现吉非替尼治疗的反应与这些患者特征和EGFR突变密切相关。此外，据报道，亚洲患者的EGFR突变比西方人更频繁。我们假设存在一些基因与这种民族突变发生率的差异相关，通过基因芯片法对全基因组进行SNP分析，对这些相关基因进行鉴定。结果：我们采集了64例EGFR突变患者的血液样本，提取DNA，使用SNP Array 6.0分析全基因组SNP，确定了超过90万个位点的SNP。我们用这种方法发现了两个与EGFR激活突变相关的位点。我们正计划用其他样品组重新检验。