Integrated genomic characterization of endometrial carcinoma.
Integrated genomic characterization of endometrial carcinoma.
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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基因组、转录和蛋白质组学的综合表征。子宫浆液性肿瘤和∼25%的高级别子宫内膜样瘤具有广泛的拷贝数改变、很少的DNA甲基化改变、低雌激素受体/孕激素受体水平和频繁的TP53突变。大多数子宫内膜样瘤几乎没有拷贝数改变或TP53突变，但PTEN、CTNNB1、PIK3CA、ARID1A和KRAS突变以及SWI/SNF染色质重塑复合体基因ARID5B的新突变是常见的突变。我们鉴定的子宫内膜样瘤的一个亚组有显著增加的颠换突变频率和新发现的POL热点突变。我们的结果将子宫内膜癌分为四种类型：极点超突变、微卫星不稳定性高突变、拷贝数低和拷贝数高。子宫浆液性癌与卵巢浆液性和基底细胞样乳腺癌具有共同的基因组特征。我们证明，子宫内膜癌的基因组特征允许重新分类，这可能会影响患有侵袭性肿瘤的女性术后的辅助治疗。本文的在线版本(doi：10.1038/Nature12113)包含补充材料，授权用户可以使用。对数百例子宫内膜癌进行的综合基因组分析表明，少数肿瘤样本带有拷贝数改变或TP53突变，许多样本包含关键的癌症相关基因突变，如参与经典通路和染色质重塑的基因突变；建议将子宫内膜癌重新分类为四种不同的类型，这可能会对患者的治疗方案产生影响。本文的在线版本(doi：10.1038/Nature12113)包含补充材料，授权用户可以使用。这篇来自癌症基因组图谱研究网络的论文对350多名患者的子宫内膜癌进行了深入的全基因组分析。基于一系列基因组特征，包括新发现的DNA聚合酶基因极点突变和ARID5B DNA结合蛋白新突变，作者提出了将子宫内膜肿瘤重新分类为四种不同类型。这可能对患有侵袭性肿瘤的女性术后辅助治疗有临床意义。本文的在线版本(doi：10.1038/Nature12113)包含补充材料，授权用户可以使用。
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. The online version of this article (doi:10.1038/nature12113) contains supplementary material, which is available to authorized users. An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes. The online version of this article (doi:10.1038/nature12113) contains supplementary material, which is available to authorized users. This paper from The Cancer Genome Atlas Research Network presents an in-depth genome-wide analysis of endometrial (uterine) carcinomas from more than 350 patients. Based on a series of genomic features including newly identified hotspot mutations in the DNA polymerase gene POLE, and novel mutations in the ARID5B DNA-binding protein, the authors propose a reclassification of endometrial tumours into four distinct types. This might have clinical relevance for post-surgical adjuvant treatment of women with aggressive tumours. The online version of this article (doi:10.1038/nature12113) contains supplementary material, which is available to authorized users.
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