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。

abstractsObjective: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 BRAF V600E 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.