Mutations within the tyrosine kinase domain of EGFR gene specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking.
Mutations within the tyrosine kinase domain of EGFR gene specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking.
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DOI：
10.1038/sj.bjc.6603040
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发表时间：
2006-03-27
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
肺癌中表皮生长因子受体（EGFR）基因的体细胞获得性突变与吉非替尼（一种靶向EGFR的酪氨酸激酶抑制剂）的显著临床反应相关。我们在469例肺癌患者的切除肿瘤中筛选了EGFR，其中包括322例腺癌，102例鳞状细胞癌，27例大细胞癌，13例小细胞癌和5种其他细胞类型。在特定条件下进行PCR以鉴定外显子19中的任何缺失，同时进行多等位基因特异性扩增以鉴定外显子21的密码子858中的突变。EGFR突变在腺癌136例（42.2%）、大细胞癌1例和多形性癌1例中检出。外显子19的框内缺失62例，L 858 R突变77例。在322例腺癌患者中，这些突变在女性中比男性更常见（P=0.0004），在高分化肿瘤中比在低分化肿瘤中更常见（P=0.0014），在从不吸烟的患者中比在当前/以前吸烟的患者中更常见（P<0.0001）。这种突变在吸烟量超过20包/年的患者和在诊断肺癌前至少20年戒烟的患者中更常见。K-ras基因突变在吸烟者中比从不吸烟者更常见，在高剂量吸烟者中比低剂量吸烟者更常见。总之，EGFR酪氨酸激酶结构域内的突变被发现特别发生在低暴露于烟草吸烟的肺腺癌患者中。
Somatically acquired mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer are associated with significant clinical responses to gefitinib, a tyrosine kinase inhibitor that targets EGFR. We screened the EGFR in 469 resected tumours of patients with lung cancer, which included 322 adenocarcinomas, 102 squamous cell carcinomas, 27 large cell carcinomas, 13 small cell carcinomas, and five other cell types. PCR with a specific condition was performed to identify any deletion in exon 19, while mutant-allele-specific amplification was performed to identify a mutation in codon 858 of exon 21. EGFR mutations were found in 136 cases (42.2%) with adenocarcinoma, in one case with large cell carcinoma, and in one case with pleomorphic carcinoma. An in-frame deletion in exon 19 was found in 62 cases while an L858R mutation was found in 77 cases. In the 322 cases with adenocarcinoma, these mutations were more frequently found in women than in men (P=0.0004), in well differentiated tumours than in poorly differentiated tumours (P=0.0014), and in patients who were never smokers than in patients who were current/former smokers (P<0.0001). The mutation was more frequently observed in patients who smoked ⩽20 pack-year, and in patients who quit at least 20 years before the date of diagnosis for lung cancer. The K-ras mutations were more frequently found in smokers than in never smokers, and in high-dose smokers than in low-dose smokers. In conclusion, the mutations within the tyrosine kinase domain of EGFR were found to specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
158.5
作者：
Kobayashi, S;Boggon, TJ;Halmos, B
通讯作者：
Halmos, B
影响因子：
45.3
作者：
Mitsudomi, T;Kosaka, T;Yatabe, Y
通讯作者：
Yatabe, Y
影响因子：
45.3
作者：
Han, SW;Kim, TY;Kim, NK
通讯作者：
Kim, NK