Correlation between the erbB family gene mutation and clinico-pathological factors, in lung cancer.

表皮生长因子（EGFR）酪氨酸激酶抑制剂吉非替尼和厄洛替尼被认为是治疗肺癌的有效药物。2004年，我们与Dana Farber癌症研究所合作，在肺癌标本中发现EGFR激酶结构域的体细胞突变。这些突变与吉非替尼体外和体内敏感性相关。我们已经建立了灵敏的基因分型测定法（Taq-Man; Lung cancer：2005：50：375-384和LightCycler; Cl in Cancer Res：2005：11：2924-2929）以检测来自临床样品的这些EGFR突变。使用这些检测，我们已经评估了突变状态和临床病理背景。我们还评估了EGFR 20号外显子突变，即吉非替尼治疗的耐药突变。我们还进行了FISH分析，以检查EGFR扩增状态。同时检测了erbB 3和erbB 4基因的表达和突变情况，但未发现erbB 3和erbB 4基因突变。我们与Dana Farber癌症研究所合作，使用SNP阵列检测了大规模肺癌样本的基因突变状态。研究结果发表在Nature Genetics（2007：39：347-351）

Epidermal growth factor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib were approver for treatment of lung cancers. In 2004, we collaborated with Dana Farber Cancer Institute and found the EGFR somatic mutations at kinase domain from lung cance samples. The mutations were correlated with gefitinib sensitivity in vitro and in vivo. We have established the sensitive genotyping assays (Taq-Man; Lung cancer : 2005: 50: 375-384 and LightCycler; Cl in Cancer Res: 2005: 11: 2924-2929) to detect these EGFR mutations from clinical samples. Using these assays, we have evaluated the mutation status and clinico-pathological background. We have also evaluated the EGFR mutations at exon 20, as known as resistant mutant for gefitinib therapy. We have also performed the FISH analysis to examine the EGFR amplification status. ErbB3 and erbB4 expression and mutation were also examined, however, we did not find and erbB3 or erbB4 mutation. We have cont inued the collaboration with Dana Farber Cancer Institute and using the SNP array, we examined the gene mutation statuses for large scale lung cancer samples. The results were published at Nature Genetics (2007: 39: 347-351)