Epidermal growth factor receptor mutations are associated with gefitinib sensitivity in non-small cell lung cancer in Japanese
Epidermal growth factor receptor mutations are associated with gefitinib sensitivity in non-small cell lung cancer in Japanese
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DOI：
10.1016/j.lungcan.2005.08.006
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发表时间：
2006-01-01
期刊：
影响因子：
5.3
通讯作者：
Yasumoto, K
中科院分区：
文献类型：
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作者：
Uramoto, H;Sugio, K;Yasumoto, K
蛋白激酶家族是在人类癌症中发现的最频繁突变的基因家族。吉非替尼是一种表皮生长因子受体（EGFR）的ATP竞争性抑制剂，对肺腺癌和无吸烟史的患者也特别有效。为了确定对吉非替尼敏感的肺肿瘤是否包含EGFR酪氨酸激酶（TK）结构域的突变，我们筛选了20例接受吉非替尼治疗的非小细胞肺癌（NSCLC）患者肿瘤EGFR的18-23外显子。9例（45%）肿瘤有TK结构域突变。在腺癌中观察到所有突变。9例突变型病例中7例（77.8%）对吉非替尼敏感，而11例野生型病例中无一例对吉非替尼敏感。从未吸烟的患者（5/8或62.5%）比吸烟者（4/12或33.3%）更常观察到此类突变。EGFR突变患者的预后较野生型患者好（p=0.033）。这些数据表明，从不吸烟的患者的腺癌包括对吉非替尼治疗敏感的NSCLC患者的特定子集。(C)2005爱思唯尔爱尔兰有限公司保留所有权利。
The protein-kinase family is the most frequently mutated gene family found in human cancer. Gefitinib, an ATP-competitive inhibitor of epidermal growth factor receptor (EGFR), also appears to be particularly effective in adenocarcinoma of the lung and in patients without smoking history. To determine whether lung tumors sensitive to gefitinib contained mutations within the tyrosine kinase (TK) domain of EGFR, we screened exons 18-23 of EGFR of tumors in 20 patients with non-small cell lung cancer (NSCLC) who had been treated with gefitinib. Nine (45%) tumors had TK domain mutations. All mutations were observed in adenocarcinoma. Seven (77.8%) of 9 cases with mutated types showed sensitivity to gefitinib, while no cases of 11 with wild type showed gefitinib sensitivity. Such mutations were more frequently observed in patients who had never smoked (5/8 or 62.5%) than in smokers (4/12 or 33.3%). The patients with mutations of EGFR to have a more favorable prognosis than those with wild type (p=0.033). These data show that adenocarcinomas from patients who had never smoked comprise a specific subset of patients with NSCLC sensitive to gefitinib treatment. (C) 2005 Elsevier Ireland Ltd. All rights reserved.