Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer  

作　　者：Caixia Ren Yan Liu Yuxiang Wang Yan Tang Yawei Wei Congrong Liu Hongquan Zhang 

机构地区：[1]Key Laboratory of Carcinogenesis and Translational Research,Ministry of Education,and State Key Laboratory of Natural and Biomimetic Drugs,Peking University Health Science Center,Beijing 100191,China [2]Department of Human Anatomy,Histology and Embryology,Peking University Health Science Center,Beijing 100191,China [3]Department of Pathology,Peking University Health Science Center,Beijing 100191,China [4]Department of Human Anatomy,Basic Medical College of Hebei North University,Zhangjiakou 075000,China

出　　处：《Cancer Biology & Medicine》2020年第2期458-467,共10页癌症生物学与医学（英文版）

基　　金：grants from the National Key Research and Development Program of China to CL(grant No.2018 YFC1004002);National Natural Science Foundation of China(grant Nos.81730071,81472734 and 81321003 to HZ and 81402388 to CR);Natural Science Foundation of Beijing Municipality(grant No.7162102 to YW and 7171005 to HZ);Ministry of Science and Technology of China(grant No.2016 YFC 1302103 to HZ);Leading Academic Discipline Project of Beijing Education Bureau(grant No.BMU 20110254 to CR);the 111 Project of the Ministry of Education,Peking University(grant No.BMU 2018 JC004 to HZ and BMU 20150492 to CR).

摘　　要：Objective:Lynch syndrome(LS)predisposes patients to early onset endometrioid endometrial cancer(EEC).However,little is known about LS-related EEC in the Chinese population.The aim of this study was to investigate the prevalence of LS and to identify the specific variants of LS in Chinese patients with EEC.Methods:We applied universal immunohistochemistry screening to detect the expression of mismatch repair(MMR)proteins,which was followed by MLH1 methylation analysis to identify suspected LS cases,next-generation sequencing(NGS)to confirm LS,and microsatellite instability(MSI)analysis to verify LS.Results:We collected 211 samples with EEC.Twenty-seven(27/211,12.8%)EEC cases had a loss of MMR protein expression.After MLH1 methylation analysis,16 EEC cases were suggested to be associated with LS.Finally,through NGS and MSI analysis,we determined that 10 EEC(10/209,4.78%)cases were associated with LS.Among those cases,3 unreported mutations(1 frameshift and 2 nonsense)were identified.M SH6 c.597_597delC,found in 4 patients,is likely to be a founder mutation in China.Conclusions:We demonstrated the feasibility of a process for LS screening in Chinese patients with EEC,by using universal immunohistochemistry screening followed by MLH1 methylation analysis and confirmation through NGS and MSI analysis.The novel mutations identified in this study expand knowledge of LS.

关 键 词：DNA mismatch repair endometrial endometrioid cancer germline mutation Lynch syndrome next-generation sequencing 

分 类 号：R737.33[医药卫生—肿瘤]