甲状腺滤泡癌中DICER1突变的临床病理学意义  

Clinicopathological significance of DICER1 mutation in follicular thyroid carcinoma

作　　者：李雪晴 王玉莲 张真 赵钧生 孔维懋 潘星竹 鲍龙女 杨孔正 谷海燕[1] 王继纲[1] Li Xueqing;Wang Yulian;Zhang Zhen;Zhao Junsheng;Kong Weimao;Pan Xingzhu;Bao Longnü;Yang Kongzheng;Gu Haiyan;Wang Jigang(Department of Pathology,the Affiliated Hospital of Qingdao University,Qingdao 266555,China;Department of Pathology,Jining First People′s Hospital,Jining 272508,China;Department of Radiation Oncology,Qingdao Central Hospital,University of Health and Rehabilitation Sciences,Qingdao 266042,China;Department of Pathology,Qingdao West Coast New Area People′s Hospital,Qingdao 266400,China;Department of Pathology,School of Basic Medicine,Qingdao University,Qingdao 266071,China;Department of Clinical Medicine,Qingdao Medical College of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院病理科,青岛266555 [2]济宁市第一人民医院病理科,济宁272508 [3]康复大学青岛中心医院肿瘤放疗科,青岛266042 [4]青岛市西海岸新区人民医院病理科,青岛266400 [5]青岛大学基础医学院病理学系,青岛266071 [6]青岛大学青岛医学院临床医学系,青岛266003

出　　处：《中华病理学杂志》2025年第3期250-258,共9页Chinese Journal of Pathology

基　　金：山东省泰山学者人才工程(tsqn202211376);希思科-臻和肿瘤精准治疗研究基金(Y-2019 genecast-020)。

摘　　要：目的探讨甲状腺滤泡癌(follicular thyroid carcinoma,FTC)中DICER1突变的临床病理学意义。方法收集青岛大学附属医院2009—2023年间68例原发性FTC手术标本,通过Sanger测序检测所有病例中DICER1以及TERT启动子突变情况,对于突变病例进一步检测KRAS、HRAS、NRAS的突变情况,分析DICER1突变FTC的临床特点及病理学特点,并研究DICER1突变与TERT启动子突变、RAS突变的关系。结果共16例(23.5%,16/68)FTC检测到DICER1的突变;其中11例位于第25号外显子E1813附近,6例位于第24号外显子D1709附近,1例位于第25号外显子剪切区;有2例发生2种类型突变;DICER1突变FTC患者全为女性,与非突变FTC相比,平均年龄更小,微小浸润型占比更高;进一步对其中9例DICER1突变FTC检测了癌旁组织或淋巴结组织,但均未检测到DICER1突变;所有DICER1突变病例均未检测到TERT启动子及RAS热点突变;在6例DICER1野生型FTC中检测到TERT启动子突变(8.8%,6/68),其中3例伴发RAS热点突变,并表现出高侵袭性的生物学行为。结论FTC中存在DICER1突变,且可能与RAS突变、TERT突变互斥,可将其作为RAS样突变进行进一步研究。Objective To investigate the clinical and pathological significance of the DICER1 mutation in follicular thyroid carcinoma(FTC).Methods Sixty-eight cases of primary FTC resected between 2009 and 2023 were retrieved from The Affiliated Hospital of Qingdao University,Qingdao,China.Sanger sequencing was performed to identify DICER1 and TERT promoter mutations in all cases.Cases with DICER1 or TERT promoter mutations were subject to additional examination of potential mutations in KRAS,HRAS,and NRAS.The clinical and pathological features of DICER1-mutant FTCs were then analyzed.The relationship between DICER1 mutations and TERT-promoter/RAS mutations was also assessed.Results DICER1 mutations were detected in 16 of the 68 FTC cases(23.5%),with 11 near E1813 at exon 25,6 near D1709 at exon 24,and 1 in the splice region of exon 25.Two cases harbored two(distinct)mutations.All patients with DICER1-mutant FTC were female.Compared with patients with DICER1-wild-type FTC,those with DICER1-mutant were much younger,and had a higher proportion of minimally invasive subtype.Nine FTCs with DICER1 mutations were subject to further sequencing on adjacent non-cancerous tissues or lymph node tissues,but no mutations were detected.TERT-promoter or RAS hotspot mutations were not identified in any of the DICER1-mutant cases.However,TERT-promoter mutation was found in 6 DICER1-wild-type cases(8.8%,6/68),with 3 cases also having RAS hotspot mutations and exhibiting highly aggressive biological behaviors.Conclusion DICER1 mutations may occur in FTCs and appear mutually exclusive with RAS and TERT-promoter mutations,warranting further study as RAS-like mutations.

关 键 词：甲状腺肿瘤 突变 病理学 临床 DICER1 TERT RAS 

分 类 号：R73[医药卫生—肿瘤]