二代测序在子宫内膜癌分子分型的临床应用

Clinical Application of the Next Generation Sequencing for Molecular Classification in Endometrial Carcinomas

[目的]为了探索杂交捕获二代测序技术在子宫内膜癌分子亚型的临床应用。[方法]收集中山大学附属肿瘤医院经病理确诊的子宫内膜癌112例,均进行基于1021个基因panel的杂交捕获二代测序检测,分析各分子亚型的分子变异谱及与临床病理特征之间的关系。[结果]DNA聚合酶ε(POLE)突变型8例(7.1%),错配修复功能缺陷型34例(30.4%),TP53突变型26例(23.2%),非特异性分子谱型44例(39.3%),4个亚型肿瘤突变负荷中位数分别为252.0、38.4、5.8及5.4 Muts/Mb。子宫内膜癌各分子亚型之间与患者临床分期、肌层浸润深度及是否有脉管内癌栓与淋巴结转移等临床病理特征无统计学差异。PTEN(75.5%)、PIK3CA(66.7%)、ARID1A(55.9%)、TP53(40.2%)、NF1(29.4%)为子宫内膜癌最常见的突变。[结论]对子宫内膜癌进行二代测序,可同时获悉其分子分型各项指标,有效筛查Lynch综合征、各亚型分子变异谱、为免疫治疗及靶向治疗提供指导,并有助于分子遗传特征的进一步积累及探索。

[Objective]To explore the clinical application of molecular classification in endometrial cancers with the next generation sequencing(NGS).[Methods]Totally 112 cases of endometrial carcinoma diagnosed by pathology in The Sun Yat-sen University Cancer Center were collected.All of them were tested by hybridized-capture second-generation se⁃quencing based on 1,021 gene panel.The molecular variation spectrum of each subtype and its relationship between the clinicopathological features were analyzed.[Results]The cases were distributed as follows:8(7.1%)POLE mutation,34(30.4%)mismatch repair deficient,26(23.2%)TP53 mutation,44(39.3%)non-specific molecular profile.The median tumor mutation burden was respectively 252.0,38.4,5.8 and 5.4 Muts/Mb.There were no significantly differences among four subtypes in clinicopathological features such as age,histological grade,lymph node metastasis and clinical stage.PTEN(75.5%),PIK3CA(66.7%),ARID1A(55.9%),TP53(40.2%),NF1(29.4%)were the most common mutations in endometrial cancers.[Conclusions]The utilization of NGS in endometrial cancers can simultaneously identify molecular subgroups,screen Lynch syndrome and obtain molecular variation spectrum,which can provide guidance for immunothera⁃py and targeted therapy,contribute to further accumulation and exploration of molecular genetic characteristics.