靶向测序技术检测下生殖道细胞学标本确认子宫内膜癌基因突变的潜在价值  

The potential diagnostic value of targeted sequencing for detecting endometrial carcinoma mutations using cytology specimens from lower genital tract

作　　者：王轶男 杜辉[2] 戴文魁 张文勇 吴瑞芳[2] WANG Yi'nan;DU Hui;DAI Wenkui;ZHANG Wenyong;WU Ruifang(School of Medicine,Southern University of Science and Technology,Shenzhen 518055,China;Department of Obstetrics and Gynecology,Peking University Shenzhen Hospital,Shenzhen,Institute of Obstetrics and Gynecology,Shenzhen Peking University-Hong Kong University of Science and Technology(PKU-HKUST)Medical Center,Shenzhen 518035,China)

机构地区：[1]南方科技大学医学院,深圳518055 [2]北京大学深圳医院妇产中心(深圳北京大学香港科技大学医学中心妇产科学研究所),深圳518035

出　　处：《中国妇产科临床杂志》2024年第6期517-520,共4页Chinese Journal of Clinical Obstetrics and Gynecology

基　　金：深圳市基础研究重点项目(JCYJ20220818102811025);深圳市生物医药产业重大公共服务平台和核心技术攻关专项(XMHT20220104049);北京大学深圳医院科研基金(KYQD2022209、KYQD2021075)。

摘　　要：目的探讨下生殖道细胞学标本用于检测子宫内膜癌突变的可行性及适用于中国女性的靶向基因集。方法本研究纳入子宫内膜癌患者34例,采用靶向测序检测下生殖道脱落细胞标本(脱落细胞组)和子宫内膜癌组织(肿瘤组织组)中的突变。脱落细胞组包括患者经阴道自取和医生在宫颈取样的标本。比较不同采样方法检出突变的一致性。根据致病突变频率结合文献调研选取靶向基因集。结果脱落细胞组和肿瘤组织组突变检出率分别为93.55%(29/31)和100%(34/34),突变检出的Kappa一致性为0.860。脱落细胞组致病突变检出率(54.84%,17/31)低于肿瘤组织组(85.29%,29/34),差异有统计学意义(P=0.007)。医生取样的标本合格率(85.29%,29/34)高于阴道自取(52.94%,18/34),差异有统计学意义(P=0.004),两者的突变检出率和致病突变检出率差异均无统计学意义(P=0.731和P=0.474)。PIK3CA、PETN、TP53、ARID1A、CTNNB1、KRAS、MTOR和NF1这8个基因累计在医生取样和阴道自取样的致病突变率分别为93.75%和100.00%。结论下生殖道细胞学标本可用于检测子宫内膜癌突变,其中PIK3CA、PETN、TP53、ARID1A、CTNNB1、KRAS、MTOR和NF1可构建在中国女性中具有高突变检出率的靶向基因集。Objective This study aimed to investigate the feasibility of using cytology specimens from the lower genital tract to detect mutations in endometrial carcinoma(EC)and to identify a targeted gene panel suitable for Chinese women.Methods A total of 34 patients diagnosed with EC were recruited.Targeted sequencing was employed to detect mutations using cytology specimens from the lower genital tract(cytology specimen group)and surgically resected specimens(tumor group).The collection methods of cytology specimens from the lower genital tract included self-collection by patients through the vagina(vaginal self-sampling)and cervical specimens taken by doctors(clinician-sampling).The consistency of detected mutations between different sampling methods was compared.A targeted gene panel was selected based on the frequency of pathogenic mutations and literature research.Results The mutation detection rates were 93.55%(29/31)for cytology specimen group and 100%(34/34)for the tumor group(Kappa=0.860).However,the pathogenic mutation detection rate of cytology specimen group(54.84%,17/31)was lower than that of the tumor group(85.29%,29/34;P=0.007).Moreover,the pass rate of clinician-sampling(85.29%,29/34)was higher than that of self-sampling(52.94%,18/34;P=0.004).There were no statistically significant differences between these two methods regarding mutation detection rates(P=0.731)and pathogenic mutation detection rates(P=0.474).The cumulative pathogenic mutation rates of PIK3CA,PETN,TP53,ARID1A,CTNNB1,KRAS,MTOR,and NF1 were 93.75%and 100.00%for clinician-sampling and self-sampling,respectively.Conclusions Cytology specimens from the lower genital tract can be used for detecting mutations in EC.A small gene set,including PIK3CA,PETN,TP53,ARID1A,CTNNB1,KRAS,MTOR,and NF1,can achieve an excellent pathogenic mutation detection rate in Chinese EC patients.

关 键 词：子宫内膜癌 自取样 医生取样 靶向测序 阴道宫颈脱落细胞 

分 类 号：R737.33[医药卫生—肿瘤]