子宫癌肉瘤的综合分子特征分析
Integrated Molecular Characterization of Uterine Carcinosarcoma.
作者信息
Cherniack Andrew D, Shen Hui, Walter Vonn, Stewart Chip, Murray Bradley A, Bowlby Reanne, Hu Xin, Ling Shiyun, Soslow Robert A, Broaddus Russell R, Zuna Rosemary E, Robertson Gordon, Laird Peter W, Kucherlapati Raju, Mills Gordon B, Weinstein John N, Zhang Jiashan, Akbani Rehan, Levine Douglas A
机构信息
The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Van Andel Research Institute, Center for Epigenetics, Grand Rapids, MI 49503, USA.
出版信息
Cancer Cell. 2017 Mar 13;31(3):411-423. doi: 10.1016/j.ccell.2017.02.010.
We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.
我们对子宫癌肉瘤（UCS）进行了基因组、表观基因组、转录组和蛋白质组特征分析。队列样本存在广泛的拷贝数改变和高度复发的体细胞突变。在TP53、PTEN、PIK3CA、PPP2R1A、FBXW7和KRAS中发现了频繁突变，这与子宫内膜样癌和浆液性子宫癌相似。转录组测序在一部分病例中鉴定出了强烈的上皮-间质转化（EMT）基因特征，这归因于微小RNA启动子处的表观遗传改变。通过癌症基因组图谱研究的所有肿瘤类型中，UCS的EMT评分范围最大。UCS与具有中间EMT特征的妇科癌和肉瘤具有共同的蛋白质组特征。还鉴定出了作为治疗靶点的基因中的多个体细胞突变和拷贝数改变。
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