荧光原位杂交法检测非小细胞肺癌患者ROS1基因重排及其与临床病理特征的关系

摘要

目的 探讨非小细胞肺癌(NSCLC)患者中ROS1基因的重排情况,并分析其与临床病理特征的关系.方法 采用荧光原位杂交(FISH)法检测1 652例NSCLC组织中ROS1基因的重排;提取FISH检测重排阳性样本RNA,应用逆转录聚合酶链反应扩增后,Sanger法测序并分析ROS1融合基因情况.结果 在1 652例NSCLC患者中,ROS1基因重排53例(3.2％),其中CD74-ROS1重排15例,SLC34A2-ROS1重排13例,SDC4-ROS1重排13例,TPM3-ROS1重排12例.无吸烟史患者ROS1基因重排阳性49例,有吸烟史(轻度或重度)患者ROS1基因重排4例,差异有统计学意义(P＜0.05).ROS1基因重排更容易发生在年轻患者中(P＜0.05),组性别差异无统计学意义(P＞0.05).ROS1基因重排只发生在腺癌中,不同临床分期患者的ROS1基因重排的发生率差异有统计学意义(P＜0.05).结论 ROS1基因重排具有多样性,代表了NSCLC新的分子亚型.ROS1重排更易发生在年轻、不吸烟的腺癌患者中.%Objective To detect the frequency of ROS1 gene rearrangement in non-small cell lung cancer (NSCLC) patients by FISH,and to analyze the relationship between ROS1 gene rearrangement and clinical features (including age,sex,stage,histology,smoking history) with NSCLC.Methods The ROS1 gene rearrangement in histological sections of 1 652 NSCLC tissues was detected by FISH.The extracted RNA was amplified and the sequences were analyzed by Sanger sequencing for ROS1-positive samples.Results ROS1 rearrangement was identified in 53 specimens (3.2％) from the 1 652 NSCLC tissues.Among these positive cases,15 were CD74-ROS1,13 were SLC34A2-ROS1,13 were SDC4-ROS1 and 12 were TPM3-ROS1.The frequency of ROS1 rearrangement was significantly higher in never-smoking patients (49 cases) than in smokers (4 cases) (P ＜0.05).Patients with ROS1-positive NSCLC tended to be younger and there was no significant difference in sex (P ＞ 0.05).All of the ROS1-positive samples were adenocarcinomas,with a tendency toward higher clinical stage (P ＜ 0.05).Conclusions ROS1 rearrangement has diversity,and may be defined as a new molecular subtype of NSCLC.ROS1 rearrangement tends to occur in younger,and never-smoker lung adenocarcinoma patients.