摘要目的：探讨非小细胞肺癌中常见驱动基因突变的特点及其与临床病理特征的关系。方法采用蝎形探针扩增阻滞突变系统（ scorpions ARMS）荧光定量PCR对205例原发性非小细胞肺癌手术切除标本进行驱动基因突变检测，并结合临床病理资料分析驱动基因存在情况及其与患者临床病理特征的关系。结果205例非小细胞肺癌中，共检测到146例存在基因突变（71．2％），肺腺癌驱动基因总突变率达81．7％（138／169），分别为表皮生长因子受体（ EGFR，63．3％，107／169）、KRAS （5．9％，10／169）、PIK3CA（4．1％，7／169）、间变性淋巴瘤激酶（ALK，4．1％，7／169）、ROS1（3．0％，5／169）、RET（3．6％，6／169）、HER2（1．8％，3／169）、NRAS（0．6％，1／169）和BRAF（0．6％，1／169）。在非小细胞肺癌患者群体中，腺癌（P＜0．01）、女性（P＝0．003）、无吸烟史（P＜0．01）患者驱动基因总突变率比非腺癌、男性、有吸烟史患者的突变率高，与患者的年龄（ P＝0．281）和病理分期（ P＝0．490）无关。 EGFR突变更容易发生在腺癌（ P＜0．01）、女性（ P＜0．01）、无吸烟史（ P＝0．002）、≥62岁（P＝0．012）患者中。 EGFR突变率在鳞屑样为主型、腺泡样为主型、乳头状为主型、微小乳头状为主型腺癌更高，与病理分期（ P＝0．237）无关。 KRAS突变率在实性为主型和浸润性黏液腺癌更高（ P＝0．015）。在腺癌中，≥62岁、浸润性黏液腺癌和胎儿型腺癌患者的PIK3CA突变率更高（ P值分别为0．015，0．006）。 ALK、ROS1、RET融合基因总阳性率在实性为主型和浸润性黏液腺癌的非吸烟患者中更高（P值分别为0．012，0．017），ALK重排更容易发生在病理分期较早、实性为主型和浸润性黏液腺癌中（P值分别为0．025，0．014），ROS1重排更容易发生在浸润性黏液腺癌中（P＝0．049）。NRAS、BRAF、HER2突变发生率低，其临床意义有待探讨。结论中国非小细胞肺癌患者常见驱动基因突变与临床病理特征的关系具有多样性，其中女性、无吸烟史的肺腺癌患者突变率较高。

abstractsObjective To study the relationship between mutations of well-known driver genes and clinicopathologic characteristics of non-small cell lung cancers ( NSCLC ) . Methods Scorpions amplification refractory mutation system ( scorpions ARMS) fluorescence quantitative PCR was performed to investigate 205 driver gene mutation status in NSCLC in correlation with clinicopathological characteristics of the patients.Results Driver gene mutations were detected in 146 of 205 (71.2%) patients with NSCLC, including 81.7%( 138/169 ) adenocarcinomas, in which mutations of nine genes were found:EGFR (63.3%,107/169), KRAS (5.9%,10/169), PIK3CA (4.1%,7/169), ALK (4.1%,7/169), ROS1 (3.0%,5/169), RET (3.6%,6/169), HER2 (1.8%,3/169), NRAS (0.6%,1/169) and BRAF (0.6%,1/169).The frequencies of driver gene mutations were higher in adenocarcinomas, female patients and non-smokers (P<0.01, P=0.003, P<0.01, respectively).Driver gene mutation status showed no correlation with either the age or the clinical stage (P=0.281, P=0.490, respectively).However, EGFR mutations tended to occur in adenocarcinoma, female, non-smokers, and patients of≥62 years of age ( P<0.01, P<0.01, P=0.002, P=0.012, respectively) .The frequency of EGFR mutation was positively correlated with the tumor histology of lepidic, acinar, papillary and micropapillary predominant growth&nbsp;patterns.There was no relationship between EGFR mutation and the clinical stage ( P =0.237 ) .The frequency of KRAS mutation was higher in solid predominant and invasive mucinous adenocarcinomas ( P=0.015); that of PIK3CA mutation was higher in patients of ≥62 years of age, invasive mucinous adenocarcinoma and fetal adenocarcinoma ( P =0.015, P =0.006, respectively) .ALK, ROS1 or RET mutation positive NSCLC tended to occur in nonsmokers and have solid predominant tumors and invasive mucinous adenocarcinoma ( P=0.012, P=0.017 respectively).The frequency of EML4-ALK mutation was higher in the early stage patients with solid predominant tumors and invasive mucinous adenocarcinomas ( P=0.025, P =0.014, respectively ); that of ROS1 rearrangement was higher in invasive mucinous adenocarcinomas (P=0.049).NRAS, BRAF and HER2 gene mutations were infrequent and their clinical significance remained to be elucidated.Conclusions The relationship between mutations of well-known driver genes and clinicopathological characteristics in patients with NSCLC has diversity, the rate of mutations is higher in non-smoking female patients with adenocarcinoma.