Nature. 2013 May 2;497(7447):67-73. doi: 10.1038/nature12113.
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.
我们使用基于阵列和测序的技术对 373 例子宫内膜癌进行了综合基因组、转录组和蛋白质组学特征分析。子宫浆液瘤和大约 25%的高级别子宫内膜样肿瘤有广泛的拷贝数改变，很少有 DNA 甲基化变化，雌激素受体/孕激素受体水平低，并且频繁发生 TP53 突变。大多数子宫内膜样肿瘤有很少的拷贝数改变或 TP53 突变，但经常发生 PTEN、CTNNB1、PIK3CA、ARID1A 和 KRAS 突变，以及 SWI/SNF 染色质重塑复合物基因 ARID5B 的新突变。我们鉴定的子宫内膜肿瘤亚组具有明显增加的颠换突变频率和 POLE 中新增的热点突变。我们的结果将子宫内膜癌分为四类：POLE 超突变型、微卫星不稳定高突变型、拷贝数低型和拷贝数高型。子宫浆液性癌与卵巢浆液性癌和基底样乳腺癌具有共同的基因组特征。我们证明了子宫内膜癌的基因组特征可以进行重新分类，这可能会影响具有侵袭性肿瘤的女性手术后的辅助治疗。
