Integrated genomic characterization of endometrial carcinoma

摘要

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ～25 % of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations .Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.%来自“癌症基因组图谱研究网络”的这篇论文rn发表了对350多名患者的子宫内膜肿瘤所做rn的一项全基因组深度分析。基于一系列基因rn组特征(包括在DNA聚合酶基因POLE上新发rn现的热点突变和ARID5B DNA．结合蛋白中的rn新颖突变)，本文作者提出将子宫内膜肿瘤重rn新划分成四个不同类型。这对患有恶性肿瘤rn的妇女的术后辅助治疗也许会有临床意义。