Distinctive role of DICER1 mutations in distant metastatic thyroid cancer  

作　　者：Cong Shi Zhuanzhuan Mu Wenting Guo Xin Zhang Di Sun Yuqing Sun Hao Wang Dingding Zhang Jun Liang Yansong Lin 

机构地区：[1]Department of Nuclear Medicine,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China [2]Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine,Beijing 100730,China [3]Biomedical Engineering Facility of National Infrastructures for Translational Medicine,Institute of Clinical Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China [4]Department of Oncology,Qingdao Municipal Hospital,School of Medicine,Qingdao University,Qingdao 266011,China [5]Center for Prevention and Early Intervention,National Infrastructures for Translational Medicine,Institute of Clinical Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730,China [6]Key Laboratory of Carcinogenesis&Translational Research(Ministry of Education/Beijing),Department of Medical Oncology,Peking University Cancer Hospital&Institute,Beijing 100142,China [7]Department of Oncology,Peking University International Hospital,Beijing 102206,China

出　　处：《Chinese Journal of Cancer Research》2024年第6期700-712,共13页中国癌症研究(英文版)

基　　金：supported by the National High Level Hospital Clinical Research Funding(No.2022-PUMCHB-072)。

摘　　要：Objective:This study investigated the clinical significance of DICER1 mutations in patients with distant metastatic follicular cell-derived thyroid cancer(FDTC).Methods:This study included 310 Chinese patients with distant metastatic FDTC.We analyzed the interactions between DICER1 mutations and other gene alterations and compared the clinicopathological characteristics of patients with pathogenic(P)or likely pathogenic(LP)DICER1 mutations(n=9),other gene alterations(n=253),and no gene alterations(n=37).To compare FDTCs with different drivers,isolated BRAFV600E,RAS mutations,and RET fusions were compared with isolated DICER1 mutations.Results:The prevalence of DICER1 mutations was 6.5%(20/310)in the patient cohort.Among patients with DICER1 mutations,45%(9/20)harbored P or LP DICER1 variants and 55%(11/20)harbored DICER1 variants of uncertain significance(VUS).The coexistence of DICER1 mutations and other gene alterations was detected in65%(13/20)of patients.Compared with VUS,P or LP DICER1 variants were almost mutually exclusive with early driver alterations(such as BRAFV600E)(11.1%vs.81.8%,P=0.002)and more coexisted with late-hit events,particularly TP53 mutations(44.4%vs.27.3%,P=0.642).Clinically,compared with the no alteration and other alteration groups,the DICER1 mutation group exhibited larger primary tumors,higher poorly differentiated thyroid cancer proportion,more extrathyroidal extension,more extrapulmonary metastases,and higher radioactive iodine-refractory proportion(all P<0.05).Cases with isolated DICER1 mutations differed from those with isolated BRAFV600E and RET fusions in terms of tumor size,poorly differentiated thyroid cancer proportion,and metastatic sites,but were similar to cases with isolated RAS mutations in the high proportion of follicular thyroid cancer,N0,and extrapulmonary metastases.Conclusions:Mutation of DICER1 gene is a non-negligible molecular event and it may represent an aggressive subset of FDTCs.DICER1 has RAS-like clinical characteristics and DICER1-mutant tumors exhibit mo

关 键 词：DICER1 mutations follicular cell-derived thyroid cancer distant metastatic next-generation sequencing clinical aggressiveness 

分 类 号：R73[医药卫生—肿瘤]