Identification of molecular pathway aberrations in uterine serous carcinoma by genome-wide analyses.

我们分析了子宫浆液性癌样本的基因组，以更好地了解这种癌症的分子遗传学特征。对10例子宫浆液性癌及其配对的正常血液或组织标本进行了全外显子组测序。在76例子宫浆液性癌中，TP53(81.6%)、PIK3CA(23.7%)、FBXW7(19.7%)和PPP2R1A(18.4%)发生了频繁的体细胞突变。所有与浆液性子宫内膜上皮内癌相关的9例浆液性癌在子宫浆液性癌和同时浆液性子宫内膜上皮内癌成分之间具有一致的PIK3CA、PPP2R1A和TP53突变状态。DNA拷贝数分析显示CCNE1基因座基因组扩增频繁，FBXW7基因座缺失。在这些子宫浆液性癌中，近一半(48%)存在PIK3CA突变和/或PIK3CA扩增。

We analyzed the genomes of uterine serous carcinoma samples to better understand the molecular genetic characteristics of this cancer. Whole-exome sequencing was performed on 10 uterine serous carcinomas and the matched normal blood or tissue samples. We found frequent somatic mutations in TP53 (81.6%), PIK3CA (23.7%), FBXW7 (19.7%), and PPP2R1A (18.4%) among the 76 uterine serous carcinomas examined. All nine serous carcinomas that had an associated serous endometrial intraepithelial carcinoma had concordant PIK3CA, PPP2R1A, and TP53 mutation status between uterine serous carcinoma and the concurrent serous endometrial intraepithelial carcinoma component. DNA copy number analysis revealed frequent genomic amplification of the CCNE1 locus and deletion of the FBXW7 locus. Nearly half of these uterine serous carcinomas (48%) harbored PIK3CA mutation and/or PIK3CA amplification.