A novel EGFR mutation D1012H and polymorphism at exon 25 in Japanese lung cancer
A novel EGFR mutation D1012H and polymorphism at exon 25 in Japanese lung cancer
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DOI：
10.1007/s00432-008-0411-5
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发表时间：
2008-12-01
影响因子：
3.6
通讯作者：
Fujii, Yoshitaka
中科院分区：
文献类型：
--
作者：
Sasaki, Hidefumi;Okuda, Katsuhiro;Fujii, Yoshitaka
前言表皮生长因子受体（EGFR）基因在激酶结构域的突变已被报道在非小细胞肺癌（NSCLC）。材料与方法我们对398例手术治疗的NSCLC患者的EGFR基因C端突变和多态性进行了研究。共纳入268例腺癌病例。结果在398例肺癌患者中发现1例EGFR第25外显子突变（G3034，D1012H）。在NSCLC中EGFR C端结构域测序期间，在外显子25处确定了194例EGFR多态性（C2982T）病例。多态性状态与性别、吸烟状态（从不吸烟者vs.吸烟者）、病理亚型和EGFR突变无关。EGFR基因多态性在年轻NSCLC患者中的比例明显高于其他患者（60，45.6%，P = 0.0467）。EGFR基因多态性在淋巴结阳性NSCLC中的比例（57.4%）显著高于淋巴结阴性NSCLC（44%）（P = 0.0168）。结论EGFR基因C端突变在肺癌中极为罕见，但D1012H突变可能与EGFR功能有关。EGFR基因25号外显子多态性可能与NSCLC的进展有关。
Introduction Mutations of the epidermal growth factor receptor (EGFR) gene at kinase domain have been reported in non-small-cell lung cancer (NSCLC). However, EGFR mutations status at C-terminal domain has not been reported in detail.Materials and methods We investigated the EGFR mutation and polymorphism statuses at C-terminal domain in 398 surgically treated NSCLC cases. Two hundred and sixty-eight adenocarcinoma cases were included. The presence or absence of EGFR mutation and polymorphism was analyzed by direct sequences.Results A novel EGFR somatic mutation at exon 25 (G3034, D1012H) was found from 1 of 398 lung cancer patients. During sequencing of EGFR C-terminal domain in NSCLC, 194 EGFR polymorphism (C2982T) cases were identified at exon 25. The polymorphism statuses were not correlated with gender, smoking status (never smoker vs. smoker), pathological subtypes and EGFR mutations. The EGFR polymorphism ratio was significantly higher in younger NSCLC ( 60, 45.6%, P = 0.0467). The EGFR polymorphism ratio was significantly higher in lymph node positive NSCLC (57.4%) than in lymph node negative NSCLC (44%, P = 0.0168). In 46 total gefitinib treated NSCLC patients, exon 25 polymorphism was not correlated with prognosis.Conclusion EGFR mutation at C-terminal in lung cancers seemed to be extremely rare, however, this D1012H mutation might be a role in EGFR function. EGFR polymorphism at exon 25 might be correlated with progression of NSCLC.