Clinical significance of EML4-ALK fusion gene and association with EGFR and KRAS gene mutations in 208 Chinese patients with non-small cell lung cancer.
Clinical significance of EML4-ALK fusion gene and association with EGFR and KRAS gene mutations in 208 Chinese patients with non-small cell lung cancer.
复制标题
208例中国非小细胞肺癌患者EML4-ALK融合基因及其与EGFR和KRAS基因突变的临床意义
DOI：
10.1371/journal.pone.0052093
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Li Y;Li Y;Yang T;Wei S;Wang J;Wang M;Wang Y;Zhou Q;Liu H;Chen J
EML4-ALK融合基因最近在一小部分对ALK抑制剂有积极反应的非小细胞肺癌（NSCLC）患者中被发现。中国非小细胞肺癌患者EML4-ALK融合基因的特征尚不清楚。在这里，我们报告了208名中国非小细胞肺癌患者的EML4-ALK、EGFR状态和KRAS突变的患病率。24.5%（51/208）的患者发现EGFR突变。与先前的报道一致，这些突变在女性中被鉴定为高频率（47.5% vs 15.0%， P<0.05）；不吸烟者（42.3%比吸烟者13.9%，P<0.05）和腺癌患者（44.2%比非腺癌患者8.0%，P<0.05）。本研究组KRAS突变患者仅为2.88%（6/208）。我们发现了7例携带EML4-ALK融合基因的患者（3.37%,7/208），其中4例携带变异3(57.1%)，2例携带变异1,1例携带变异2。阳性病例均为女性（11.5%,7/61）。阳性6例为非吸烟者（7.69%,6/78）。EML4-ALK易位在女性非吸烟腺癌患者中的发生率高达15.2%（5/33）。EML4-ALK阳性患者中未检测到EGFR/KRAS突变。病理分析显示alk阳性患者的实性印戒细胞型（4/7）与黏液筛网型（3/7）无显著差异。免疫染色显示原发癌中ALK重排的肿瘤内异质性，50%（3/6）的转移性肿瘤为ALK阴性。meta分析显示，EML4-ALK易位发生率为4.84%（125/2580）的非选择性NSCLC患者，并且在非吸烟腺癌患者中也占主导地位。综上所述，EML4-ALK易位在整个非小细胞肺癌患者群体中并不常见，但在非吸烟者、腺癌患者的非小细胞肺癌亚组中却很常见。原发癌和转移癌中ALK重排存在肿瘤内异质性。
The EML4-ALK fusion gene has been recently identified in a small subset of non-small cell lung cancer (NSCLC) patients who respond positively to ALK inhibitors. The characteristics of the EML4-ALK fusion gene in Chinese patients with NSCLC are poorly understood. Here, we report on the prevalence of EML4-ALK, EGFR status and KRAS mutations in 208 Chinese patients with NSCLC. EGFR mutations were found in 24.5% (51/208) of patients. In concordance with previous reports, these mutations were identified at high frequencies in females (47.5% vs 15.0% in males; P<0.05); never-smokers (42.3% vs 13.9% in smokers; P<0.05), and adenocarcinoma patients (44.2% vs 8.0% in non-adenocarcinoma patients; P<0.05). There were only 2.88% (6/208) patients with KRAS mutations in our study group. We identified 7 patients who harbored the EML4-ALK fusion gene (3.37%, 7/208), including 4 cases with variant 3 (57.1%), 2 with variant 1, and 1 with variant 2. All positive cases corresponded to female patients (11.5%, 7/61). Six of the positive cases were non-smokers (7.69%, 6/78). The incidence of EML4-ALK translocation in female, non-smoking adenocarcinoma patients was as high as 15.2% (5/33). No EGFR/KRAS mutations were detected among the EML4-ALK positive patients. Pathological analysis showed no difference between solid signet-ring cell pattern (4/7) and mucinous cribriform pattern (3/7) in ALK-positive patients. Immunostaining showed intratumor heterogeneity of ALK rearrangement in primary carcinomas and 50% (3/6) of metastatic tumors with ALK-negative staining. Meta-analysis demonstrated that EML4-ALK translocation occurred in 4.84% (125/2580) of unselected patients with NSCLC, and was also predominant in non-smoking patients with adenocarcinoma. Taken together, EML4-ALK translocations were infrequent in the entire NSCLC patient population, but were frequent in the NSCLC subgroup of female, non-smoker, adenocarcinoma patients. There was intratumor heterogeneity of ALK rearrangement in primary carcinomas and at metastatic sites.
登录
查看更多内容
影响因子：
11.2
作者：
Sasaki T;Koivunen J;Ogino A;Yanagita M;Nikiforow S;Zheng W;Lathan C;Marcoux JP;Du J;Okuda K;Capelletti M;Shimamura T;Ercan D;Stumpfova M;Xiao Y;Weremowicz S;Butaney M;Heon S;Wilner K;Christensen JG;Eck MJ;Wong KK;Lindeman N;Gray NS;Rodig SJ;Jänne PA
通讯作者：
Jänne PA
影响因子：
5.3
作者：
Tiseo, M.;Gelsomino, F.;Ardizzoni, A.
通讯作者：
Ardizzoni, A.
影响因子：
51.1
作者：
Mitsudomi, Tetsuya;Morita, Satoshi;Fukuoka, Masahiro
通讯作者：
Fukuoka, Masahiro
影响因子：
6
作者：
Martelli, Maria Paola;Sozzi, Gabriella;Falini, Brunangelo
通讯作者：
Falini, Brunangelo
影响因子：
11.5
作者：
Govindan, R
通讯作者：
Govindan, R