甲状腺乳头状癌BRAF V600E、NRAS、TERT基因的突变特征及其与临床病理特征的相关性

Mutation of BRAF V600E,NRAS,TERT gene in papillary thyroid cancer and the correlation with clinicopathological characteristics

目的:探索甲状腺乳头状癌(papillary thyroid carcinoma,PTC)三种驱动基因BRAF V600E、NRAS和TERT基因突变与临床病理特征的相关性,旨在为甲状腺癌患者提供更精准的分子分型检测指导。方法:纳入2018年01月至2018年12月期间空军军医大学西京医院收治的接受BRAF V600E、NRAS、TERT三基因检测的PTC患者,回顾性收集患者的临床病理特征和三种基因突变状态资料,分析各基因的突变特点及其与临床病理特征的相关性。结果:本研究347例患者,BRAF V600E、TERT、NRAS基因突变率分别为89.3%、2.0%以及1.2%。TERT和NRAS基因的患者同时发现有BRAF V600E基因突变。BRAF V600E/NRAS或BRAF V600E/TERT双基因突变率为3.2%。双基因突变患者多发病灶占72.7%,病理分型非PTMC占72.7%,淋巴结转移率为81.8%。BRAF V600E/NRAS双基因突变患者均发现淋巴结转移,BRAF V600E/TERT双基因突变患者有71.4%(5/7)出现淋巴结转移。单因素分析结果显示,年龄、病灶数量、病灶位置以及淋巴结转移与基因突变相关(P均<0.05)。结论:BRAF V600E基因在PTC中的突变率达89.3%,TERT、NRAS基因突变往往与BRAF V600E基因突变同时出现,双基因突变可能与PTC侵袭性相关。

Objective:To explore the mutation characteristics of BRAF V600 E,NRAS,TERT genes and their association with clinicopathological features in thyroid cancer.Methods:Patients with thyroid cancer,admitted in Xijing Hospital,were enrolled into this study,between January 2018 and December 2018.All participants accepted BRAF V600 E,NRAS and TERT gene detection.The mutation features were analyzed,as well as their clinical association with clinical characteristics.Results:347 patients were enrolled into this study.The mutation rate of BRAF V600 E,TERT,NRAS genes were 89.3%,2.0% and 1.2%.TERT and NRAS mutation coexisted with BRAF V600 E gene mutation.Double mutation rate of BRAF V600 E/NRAS or BRAF V600 E/TERT was 3.2%.Among 72.7% with BRAF V600 E/NRAS or BRAF V600 E/TERT co-mutation,72.7% were found to be non-PTMC with multiple lesions.Lymph node metastasis rate was 81.8%.All patients with BRAF V600 E/NRAS co-mutation were found with lymph mode metastasis.71.4% patients with BRAF V600 E/TERT double mutation had metastatic lymph nodes.Single-factor analysis showed that age,number and location of lesion,lymph node metastasis were associated with double mutation(P all<0.05).Conclusion:The mutation rate of BRAF V600 E was 89.3% in PTC.TERT and NRAS were always coexisted with BRAF V600 E.Double gene mutation maybe related with the aggressiveness of PTC.