EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients
EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients
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DOI：
10.1158/0008-5472.can-05-1705
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发表时间：
2005-09-01
期刊：
影响因子：
11.2
通讯作者：
Wistuba, II
中科院分区：
文献类型：
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作者：
Tang, XN;Shigematsu, H;Wistuba, II
为了确定EGFR酪氨酸激酶结构域突变是否是肺腺癌发病机制中的早期事件，我们检测了携带常见EGFR突变的肺腺癌组织学正常支气管和细支气管上皮中EGFR突变的存在。从21个已知EGFR突变的肿瘤、16个无突变的肿瘤和来自相同手术标本的90个正常支气管和细支气管上皮的显微解剖组织中提取DNA。采用PCR和DNA直接测序技术，在21例EGFR突变腺癌患者中，9例（43%）正常呼吸道上皮中检测到与肿瘤相同的EGFR突变，而在肿瘤无突变的患者中未检测到。在肿瘤内正常上皮中的突变（43%）比邻近部位（24%）更频繁，这表明了局部场效应现象。我们的研究结果表明，EGFR酪氨酸激酶结构域的突变是肺腺癌发病机制中的早期事件，并建议EGFR突变作为早期检测标志物和化学预防靶点。
To determine whether EGFR tyrosine kinase domain mutations are early events in the pathogenesis of lung adenocarcinomas, we tested for the presence of EGFR mutations in histologically normal bronchial and bronchiolar epithelia from lung adenocarcinomas bearing the common EGFR mutations. DNA was extracted from microdissected tissue obtained from 21 tumors with known EGFR mutations, 16 tumors without mutation, and 90 sites of normal bronchial and bronchiolar epithelium from the same surgical specimens. With the use of PCR and direct DNA sequencing, EGFR mutations identical to the tumors were detected in the normal respiratory epithelium in 9 of 21 (43%) patients with EGFR mutant adenocarcinomas but none in patients without mutation in the tumors. The finding of mutations being more frequent in normal epithelium within tumor (43%) than in adjacent sites (24%) suggests a localized field effect phenomenon. Our findings indicate that mutation of the tyrosine kinase domain of EGFR is an early event in the pathogenesis of lung adenocarcinomas, and suggest EGFR mutations as an early detection marker and chemoprevention target.