中国非小细胞肺癌患者表皮生长因子受体突变的研究

背景与目的:最近的研究结果表明,表皮生长因子受体(epidermalgrowthfactorreceptor,EGFR)基因酪氨酸激酶域的体细胞突变与非小细胞肺癌(non鄄smallcelllungcancer,NSCLC)患者对酪氨酸激酶抑制剂吉非替尼的敏感性密切相关。这些突变均发生在酪氨酸激酶域的ATP结合域附近,突变为19号外显子上的缺失突变,或18和21号外显子上的替代突变。研究发现,日本患者的突变率高于美国患者的突变率。本研究中我们分析中国NSCLC患者肺癌组织中EGFR突变情况。方法:收集2004年7月到10月间中山大学肿瘤防治中心52例可手术的NSCLC患者的新鲜组织标本,包括肿瘤组织标本和来自同一患者相应的正常肺组织标本。所有患者均未接受过吉非替尼治疗。采用PCR技术扩增EGFR基因的19和21号外显子,从正反两个方向对扩增片段进行DNA测序和分析。结果:52例1NNNSCLC患者中10例(19.2%)患者EGFR基因酪氨酸激酶域存在体细胞突变。10例突变中包括7例(70%)发生于19号外显子上的缺失突变,另外3例(30%)发生于21号外显子上的替代突变。腺癌(6/23,26.1%)、腺鳞癌(2/5,40.0%)和支气管肺泡癌(2/4,50.0%)的突变率高于鳞癌(0/20,0.0%)的突变率(P=0.025);非吸烟者的突变率(7/17,41.8%)高于吸烟者的突变率(3/35,8.6%)(P=0.009);而女性患者突变率(3/13,23.1%)与男性患者突变率(7/39,18.0%)无显著性差异(P=0.697)。结论:中国NSCLC患者EGFR的突变率较高,与日本患者的突变情况相似,明显高于高加索人种。

Epidermal growth factor receptor mutation in Chinese patients with non-small cell lung cancer

BACKGROUND & OBJECTIVE: Recent studies showed that somatic mutations in epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain are assoc iated with sensitivity of non-small cell lung cancer(NSCLC) to TK inhibitor gefi tinib. The mutations, including in-frame deletions at exon 19 and substitutions at exon 18 or exon 21, cluster around ATP-binding pocket of TK domain. The frequ ence of mutations are higher in Japanese patients than in American patients. Thi s study was to analyze EGFR mutations in Chinese patients with NSCLC. METHODS: F rom Jun. to Oct. 2004, fresh specimens of lung cancer and corresponding normal l ung tissue were collected from 52 consecutive NSCLC patients (39 men and 13 wome n) treated in Cancer Center of Sun Yat-sen University. All patients had not rece ived treatment of gefitinib. DNA was extracted from the 52 specimens. Exons 19 a nd 21 were amplified by polymerase chain reaction (PCR), and sequenced and analy zed from both sense and antisense directions. RESULTS: Somatic mutations in TK d omain of EGFR in tumors were identified from 10 of the 52 (19.2%) patients, incl uding 7 cases of in-frame deletion in exon 19 and 3 cases of amino acid substitu tion in exon 21. Mutation rate was significantly higher in adenocarcinoma, adeno -squamous carcinoma, and bronchioloalveolar cancer than in squamous cell carcino ma [26.1% (6/23), 40.0% (2/5), and 50.0% (2/4) vs. 0 (0/20), P=0.025], and signi ficantly higher in non-smokers than in smokers [41.8% (7/17) vs. 8.6% (3/35), P= 0.009]. Mutation rate in women was similar to that in men [23.1% (3/13) vs. 18.0 % (7/39), P=0.697]. CONCLUSION: EGFR mutation rate in Chinese NSCLC patients is similar to that in Japanese patients, and is obviously higher than that in Cauca sian population.