L858R EGFR mutation status correlated with clinico-pathological features of Japanese lung cancer
L858R EGFR mutation status correlated with clinico-pathological features of Japanese lung cancer
复制标题
DOI：
10.1016/j.lungcan.2006.06.003
复制
发表时间：
2006-10-01
期刊：
影响因子：
5.3
通讯作者：
Fujii, Yoshitaka
中科院分区：
文献类型：
--
作者：
Sasaki, Hidefumi;Endo, Katsuhiko;Fujii, Yoshitaka
约25%-40%的日本肺癌患者存在表皮生长因子受体(EGFR)基因的体细胞突变。这些突变与临床和放射学对EGFR酪氨酸激酶抑制剂的反应有关。最常见的突变是精氨酸取代亮氨酸858位氨基酸(L858R)和外显子19缺失，尤其是缺失1型突变。我们研究了575例手术治疗的非小细胞肺癌(NSCLC)患者中的这些EGFR突变状态。研究对象为腺癌患者362例。通过基因分型分析(TaqMan分析，n=386，LightCycler分析，n=98)和序列分析(n=91)分析有无EGFR突变。在575例肺癌患者中有63例发现EGFR突变(CTG；CGG；L858R)。我们还检测了39例患者外显子19缺失1a型突变(2235-2249 del GGAATTAAGAGAAGC)和15例患者缺失1b型突变(2236-2250 del GAATTAAGAGAAGCA)。这些突变状态与性别、吸烟状况(从不吸烟者与吸烟者)以及病理亚型(腺癌与非腺癌)显著相关。L858R突变(p<；0.0001)，而不是缺失1型突变(p=0.0665)与肺癌的分化程度(好与中或差)相关。L858R突变率在非吸烟者(p=0.0496)和腺癌(p=0.0136)中显著高于缺失型突变。EGFR突变状态，尤其是L858R突变可能与吉非替尼疗效好的临床病理特征有关，如性别、吸烟史、日本肺癌病理亚型等。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
Somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in about 25-40% of Japanese lung cancer patients. These mutations are associated with clinical and radiographic responses to EGFR tyrosine kinase inhibitors. Most common mutation are arginine for leucine substitution at amino acid 858 (L858R) and exon 19 deletions, especially deletion type 1 mutation. We investigated these EGFR mutation statuses in 575 surgically treated non-small cell lung cancer (NSCLC) cases. Three-hundred and sixty-two adenocarcinoma cases were included. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis (TaqMan assay; n = 386, and LightCycler assay; n = 98) and sequences (n = 91). EGFR mutations (CTG; CGG; L858R) were found from 63 of 575 lung cancer patients. We also detected the deletion 1 a type mutations (2235-2249 del GGAATTAAGAGAAGC) from 39 patients and deletion 1b type mutations (2236-2250 del GAATTAAGAGAAGCA) from 15 patients in exon 19. These mutation statuses were significantly correlated with gender, smoking status (never smoker versus smoker), and pathological subtypes (adenocarcinoma versus non-adenocarcinoma). L858R mutation (p < 0.0001), but not deletion 1 type mutation (p = 0.0665), was correlated with differentiation status (well versus moderately or poorly) of lung cancers. L858R mutation ratio was significantly higher in non-smoker (p = 0.0496) and adenocarcinoma (p=0.0136) when compared to deletion 1 type mutations. The EGFR mutation status, especially L858R mutation might be correlated with the clinicopathological features related to good response to gefitinib, such as gender, smoking history, and pathological subtypes of Japanese lung cancers. (C) 2006 Elsevier Ireland Ltd. All rights reserved.