Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers
Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers
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DOI：
10.1093/jnci/dji055
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发表时间：
2005-03-02
影响因子：
10.3
通讯作者：
Gazdar, AF
中科院分区：
文献类型：
--
作者：
Shigematsu, H;Lin, L;Gazdar, AF
背景肺癌中表皮生长因子受体（EGFR）基因酪氨酸激酶（TK）结构域的突变与这些癌症对抑制EGFR激酶活性的药物的敏感性增加有关。然而，这种突变在肺癌发病机制中的作用尚不清楚。研究方法：我们对从617例非小细胞肺癌（NSCLC）和524例来自相同患者的正常肺组织样本以及从日本、台湾、美国和澳大利亚患者收集的36例神经内分泌肺肿瘤和243例其他上皮癌中分离的基因组DNA的EGFRTK结构域的外显子18-21进行了测序。将突变状态与临床病理特征和KRAS突变的存在进行比较，KRAS是EGFR信号通路中的一个基因，在肺癌中也经常突变。所有统计检验均为双侧检验。结果如下：我们在617例NSCLC中的130例（21%）中共检测到134个EGFR TK结构域突变，但在其他任何癌中均未检测到，在同一患者的非恶性肺组织中也未检测到。在NSCLC患者中，EGFR TK结构域突变在从不吸烟者中的发生率显著高于曾经吸烟者（51%对10%），在腺癌中显著高于其他组织学类型的癌症（40%对3%），在东亚种族患者中显著高于其他种族患者（30%对8%），在女性患者中显著高于男性患者（42%对14%;所有P
Background. Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity. However, the role of such mutations in the pathogenesis of lung cancers is unclear. Methods: We sequenced exons 18-21 of the EGFRTK domain from genomic DNA isolated from 617 non-small-cell lung cancers (NSCLCs) and 524 normal lung tissue samples from the same patients and 36 neuroendocrine lung tumors collected from patients in Japan, Taiwan, the United States, and Australia and from 243 other epithelial cancers. Mutation status was compared with clinicopathologic features and with the presence of mutations in KRAS, a gene in the EGFR signaling pathway that is also frequently mutated in lung cancers. All statistical tests were two sided. Results: We detected a total of 134 EGFR TK domain mutations in 130 (21%) of the 617 NSCLCs but not in any of the other carcinomas, nor in nonmalignant lung tissue from the same patients. In NSCLC patients, EGFR TK domain mutations were statistically significantly more frequent in never smokers than ever smokers (51% versus 10%), in adenocarcinomas versus cancer of other histologies (40% versus 3%), in patients of East Asian ethnicity versus other ethnicities (30% versus 8%), and in females versus males (42% versus 14%; all P