碘难治性甲状腺乳头状癌的基因突变特征  

Genetic mutation characteristics of iodine-refractory papillary thyroid carcinoma

作　　者：姜贝贝 尹义强 刘瑞静 刘稳 薛景丽 李敏 李培峰 Jiang Beibei;Yin Yiqiang;Liu Ruijing;Liu Wen;Xue Jingli;Li Min;Li Peifeng(Postgraduate Training Base of the 960th Hospital of the People’s Liberation Army of Jinzhou Medical University,Jinan 250031,China;Department of Pathology,the Fourth People’s Hospital of Jinan,Jinan 250031,China;Department of Pathology,the 960th Hospital of the People’s Liberation Army,Jinan 250031,China;Department of Nuclear Medicine,the 960th Hospital of the People’s Liberation Army,Jinan 250031,China)

机构地区：[1]锦州医科大学解放军第九六〇医院研究生培养基地,济南250031 [2]济南市第四人民医院病理科,济南250031 [3]解放军第九六〇医院病理科,济南250031 [4]解放军第九六〇医院核医学科,济南250031

出　　处：《临床与实验病理学杂志》2025年第1期37-43,共7页Chinese Journal of Clinical and Experimental Pathology

基　　金：山东省自然科学基金面上项目(ZR2023MH029);山东省医药卫生科技发展计划项目(202201041061)。

摘　　要：目的 探讨碘难治性甲状腺乳头状癌(radioactive iodine-refractory papillary thyroid cancer, RAIR-PTC)的基因突变特征及其与临床病理特征的相关性。方法 基于甲状腺乳头状癌(papillary thyroid cancer, PTC)基因突变特征构建PTC基因突变检测试剂盒,采用多重PCR测序对37例RAIR-PTC肿瘤样本和36例放射性碘治疗有效PTC肿瘤样本进行基因突变检测。生物信息学分析确定PTC肿瘤样本突变,并统计分析基因突变与患者临床病理特征的相关性。结果 RAIR-PTC肿瘤检测到BRAF、TERT、TP53、AKT1、NRAS等基因突变,BRAF V600E突变率为70.3%,TERT启动子突变率为24.3%。RAIR-PTC常表现为多个基因突变的累积,以BRAF或RAS和TERT启动子的共突变最为常见,而且此共突变与PTC肿瘤无进展生存显著相关。结论 基因突变的累积可促进RAIR-PTC的发生。TERT启动子突变是PTC的晚期事件,TERT启动子突变及BRAF或RAS和TERT启动子共突变有助于评估PTC患者碘难治的可能性,此特征患者应密切监测放射性碘治疗效果,尽早采取精准有效治疗。Purpose To investigate the genetic mutation characteristics and its correlation with clinicopathologic characteristics of radioactive iodine-refractory papillary thyroid cancer(RAIR-PTC).Methods PTC gene mutation detection kit was constructed based on the characteristics of PTC gene mutation.37 cases of RAIR-PTC tumor samples and 36 cases of radioiodine-avid thyroid papillary carcinoma tumor samples were detected by multiple PCR sequencing.The mutation of PTC tumor samples was identified by bioinformatics analysis,and the correlation between gene mutations and clinicopathological characteristics of patients was statistically analyzed.Results BRAF,TERT,TP53,AKT1 and NRAS gene mutations were detected in RAIR-PTC tumor samples,with BRAF V600E and TERT promoter mutation rates of 70.3%and 24.3%,respectively.Gene mutation of RAIR-PTC often manifested as the accumulation of multiple gene mutations,with co-mutations of BRAF or RAS and TERT promoter being the most common,and these co-mutations were significantly associated with patients’progression-free survival of PTC.Conclusion The accumulation of gene mutation can promote the occurrence of RAIR-PTC.TERT promoter mutation is a late event of PTC.TERT promoter mutation and co-mutations of BRAF or RAS and TERT promoter can help to evaluate the possibility of iodine refractory in PTC patients,in whom the therapeutic effect of radioactive iodine should be closely monitored and the accurate and effective treatment should be took as soon as possible.

关 键 词：甲状腺肿瘤 放射性碘治疗 基因突变 TERT启动子突变 BRAF突变 

分 类 号：R736.1[医药卫生—肿瘤]