EGFR polymorphism of the kinase domain in Japanese lung cancer
EGFR polymorphism of the kinase domain in Japanese lung cancer
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DOI：
10.1016/j.jss.2007.09.001
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发表时间：
2008-08-01
影响因子：
2.2
通讯作者：
Fujii, Yoshitaka
中科院分区：
文献类型：
--
作者：
Sasaki, Hidefumi;Endo, Katsuhiko;Fujii, Yoshitaka
背景表皮生长因子受体（EGFR）基因激酶结构域突变已在非小细胞肺癌（NSCLC）中报道，EGFR中的一些常见体细胞突变已被检测其预测吉非替尼或厄洛替尼敏感性的能力。然而，EGFR 20号外显子突变已被报道可预测吉非替尼治疗的耐药性。我们调查了303例手术治疗的非小细胞肺癌（NSCLC）患者的EGFR激酶域突变和/或多态性状态。纳入了194例腺癌病例。通过直接测序分析激酶结构域的EGFR多态性的存在或不存在。我们还调查了在国立医院组织近畿中央胸部医疗中心接受手术后接受吉非替尼治疗的23例NSCLC患者的EGFR 20号外显子多态性状态。303例肺癌患者中有75例EGFR激酶域突变。在肿瘤中EGFR酪氨酸激酶结构域测序期间，在外显子20处鉴定出86例EGFR多态性（G2607 A）。G2067 A基因多态性在非腺癌中的阳性率（37.4%）显著高于腺癌（25.3%）（P = 0.0415）。多态性状态与性别、吸烟（从不吸烟者与吸烟者）和EGFR突变无关。在46例接受吉非替尼治疗的NSCLC患者中，EGFR野生型（GG）患者的预后倾向于好于AG + AA患者。EGFR多态性在日本人肺癌中的发生率似乎低于高加索人肺癌。EGFR酪氨酸激酶基因多态性可能与肺癌的临床病理背景有关。(C)2008年爱思唯尔公司All rights reserved.
Background. Mutations of the epidermal growth factor receptor (EGFR) gene at kinase domain have been reported in non-small-cell lung cancer (NSCLC), and some common somatic mutations in EGFR have been examined for their ability to predict sensitivity to gefitinib or erlotinib. However, EGFR mutations at exon 20 have been reported to predict resistance to gefitinib therapy.Materials and methods. We investigated the EGFR mutations and/or polymorphism statuses at kinase domain in 303 surgically treated non-small cell lung cancer (NSCLC) cases. One hundred ninety-four adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of kinase domains was analyzed by direct sequences. We have also investigated EGFR polymorphism status at exon 20 for 23 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center.Results. EGFR mutations at kinase domain were found in 75 of 303 lung cancer patients. During sequencing of EGFR tyrosine kinase domain in tumors, 86 EGFR polymorphism (G2607A) cases were identified at exon 20. G2067A polymorphism was significantly higher in nonadenocarcinomas (37.4%) than in adenocarcinoma (25.3%, P = 0.0415). The polymorphism status did not correlate with gender, smoking (never smoker versus smoker), and EGFR mutations. In 46 total gefitinib treated NSCLC patients, there was a tendency toward better prognosis in EGFR wild type (GG) patients than AG + AA patients. EGFR polymorphism in Japanese lung cancers seemed to be less frequent than Caucasian lung cancers.Conclusions. EGFR-tyrosine kinase polymorphism might be associated with clinicopathological background of lung cancers. (C) 2008 Elsevier Inc. All rights reserved.