SNPに対するジーンチップによる肺癌EGFR変異遺伝子関連遺伝子の発見とその解析

肺癌是癌症死亡的主要原因，也是对治疗最具抗性的癌症之一。迄今为止，在肺肿瘤中发现了几种突变，这些突变与致瘤性、治疗靶点的相关性进行了研究。研究表明，肺癌患者肿瘤细胞中存在表皮生长因子受体（EGFR）突变，而其他器官类型的肿瘤细胞中不存在EGFR突变。吉非替尼是一种EGFR的口服酪氨酸激酶抑制剂（TKI），在日本获批，这在全球尚属首次。该药物对非小细胞肺癌患者的治疗具有重要作用，特别是具有女性，从不吸烟和腺癌组织学特征的患者。吉非替尼治疗的反应与这些患者的特征和EGFR突变密切相关。此外，据报道，亚洲人的肿瘤细胞中EGFR突变比西方人更多。基于肿瘤细胞中存在与这种突变发生率种族差异相关的基因的假设，我们进行了本研究，通过基因芯片技术对整个基因组进行SNP分析，以鉴定这些相关基因。

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 so far, which were studied in terms of the association with oncogenicity, targets of therapy. It was demonstrated that epidermal growth factor receptor (EGFR) mutation in tumor cells exists among the lung cancer patients but not among other organ type of cancer. 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, especially has characteristics that include female, never smoker, and adenocarcinoma histology. The response of treatment with gefitinib was found strongly correlated with both these patients characteristics and EGFR mutations. In addition, it was reported that there are more EGFR mutations in tumor cells of Asians than in Westerners. On the hypotheses of that there are associate genes with this ethnic difference in incidence of mutation in the tumor cells, we conducted the study to identify these associated genes by the analysis of SNP through the whole genome with Gene chip assay.