端粒酶反转录酶启动子突变在放射性碘难治性甲状腺乳头状癌中的意义  

Clinical significance of telomerase reverse transcriptase promoter mutation in radioactive iodine refractory papillary thyroid cancer

作　　者：王婷婷 蔡刚明[2] 潘懿[1] 郭鹤鸣 李思诚 马麒[4] 杨志学[5] 徐龙江[6] 胡吉[3] 方晨 Wang Tingting;Cai Gangming;Pan Yi;Guo Heming;Li Sicheng;Ma Qi;Yang Zhixue;Xu Longjiang;Hu Ji;Fang Chen(Department of Endocrinology,JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine,Wuxi 214063,China;Gene Laboratory,JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine,Wuxi 214063,China;Department of Endocrinology,the Second Affiliated of Soochow University,Suzhou 215002,China;Department of Ultrasound,the Second Affiliated of Soochow University,Suzhou 215002,China;Department of Thyroid and Breast Surgery,the Second Affiliated of Soochow University,Suzhou 215002,China;Department of Pathology,the Second Affiliated of Soochow University,Suzhou 215002,China)

机构地区：[1]江苏省原子医学研究所附属江原医院内分泌科,无锡214063 [2]江苏省原子医学研究所附属江原医院基因实验室,无锡214063 [3]苏州大学附属第二医院内分泌科,苏州215002 [4]苏州大学附属第二医院超声科,苏州215002 [5]苏州大学附属第二医院甲乳外科,苏州215002 [6]苏州大学附属第二医院病理科,苏州215002

出　　处：《中华核医学与分子影像杂志》2022年第2期90-95,共6页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：江苏省原子医学研究所青年基金(QN202007)。

摘　　要：目的:通过检测端粒酶反转录酶(TERT)启动子在放射性碘难治性甲状腺乳头状癌(RAIR-PTC)中的突变频率,探讨该基因突变对RAIR-PTC的摄碘特征及碘治疗疗效的影响。方法:对2005年1月至2020年6月在江苏省原子医学研究所附属江原医院进行放射性碘治疗的RAIR-PTC[37例,其中男15例,女22例,年龄(49.8±16.1)岁]和碘治疗有效[40例,其中男13例,女27例,年龄(39.8±10.9)岁]PTC患者的TERT启动子突变及B-Raf原癌基因丝/苏氨酸蛋白激酶(BRAF)V600E突变情况进行回顾性研究,分析不同基因突变类型的摄碘特征及碘治疗疗效差异。采用Fisher确切概率法及两独立样本t检验进行数据比较。结果:RAIR-PTC中,TERT启动子突变率为40.54%(15/37),高于碘治疗有效组(0,0/40;P<0.001),均为C228T位点突变,未发现C250T突变;而BRAF V600E突变率(64.86%,24/37)与碘治疗有效组(72.50%,29/40)比较差异无统计学意义(P=0.858)。TERT启动子突变患者年龄更大(t=3.76,P=0.001),远处转移灶不摄碘率更高(P=0.037)。启动靶向治疗者及死亡病例中TERT启动子突变患者分别占2/3和3/4。35例甲状腺球蛋白抗体(TgAb)阴性患者中,11/14的TERT启动子突变者刺激性甲状腺球蛋白(sTg)升高,而无突变组该比例为57.1%(12/21),但差异无统计学意义(P=0.357)。结论:RAIR-PTC患者中TERT启动子突变率增高,临床工作中可将该基因突变作为预测碘难治的指标之一。Objective To evaluate the influence of telomerase reverse transcriptase(TERT)promoter mutation on radioiodine uptake status of radioactive iodine refractory papillary thyroid cancer(RAIR-PTC)and radioiodine therapy response by analyzing the mutation frequency of TERT promoter in RAIR-PTC.Methods A total of 37 patients with RAIR-PTC(15 males,22 females,age(49.8±16.1)years)and 40 PTC patients with effective radioiodine therapy(13 males,27 females,age(39.8±10.9)years)between January 2005 and June 2020 in JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine were retrospectively analyzed.TERT promoter mutation and B-Raf proto-oncogene,serine/threonine kinase(BRAF)V600E mutation of patients were observed.The differences across genotype patterns on radioiodine uptake status and therapy response were compared.The Fisher′s exact test and independent-sample t test were used for data analysis.Results The incidence rate of TERT promoter mutation in the RAIR-PTC group was 40.54%(15/37,all C228T),which was significantly higher than that in the effective radioiodine therapy group(0,0/40;P<0.001).No statistically significant difference was found for the mutation rate of BRAFV600E between the RAIR group(64.86%,24/37)and the effective radioiodine therapy group(72.50%,29/40;P=0.858).Patients with TERT promoter mutation were older(t=3.76,P=0.001)and the non-intake rate of radioiodine in distant metastases of those patients was higher(P=0.037).Furthermore,2/3 of patients who received targeted therapies and 3/4 deaths had TERT promoter mutation.Among 35 patients with negative thyroglobulin antibody(TgAb),11/14 of patients with TERT mutation had a rising stimulated thyroglobulin(sTg),while the percentage of the non-TERT mutation group was 57.1%(12/21;P=0.357).Conclusion The TERT promoter mutation rate is significantly increased in RAIR-PTC patients and can serve as a prognostic predictor in RAIR.

关 键 词：甲状腺肿瘤 癌 乳头状 突变 转录启动子 端粒 末端转移酶 原癌基因蛋白质B-raf 近距离放射疗法 碘放射性同位素 

分 类 号：R736.1[医药卫生—肿瘤]