Integrated genomic analyses of ovarian carcinoma
The Cancer Genome Atlas Research Network
Affiliations Contributions Corresponding authors Journal name:
Nature Volume: 474, Pages: 609–615
Date published: (30 June 2011)
DOI: doi:10.1038/nature10166
Received 07 September 2010 Accepted 27 April 2011 Published online 29 June 2011
Abstract
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Share/bookmarkConnotea Cite U Like Facebook Twitter Delicious Digg A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.

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Nature 474 (30 Jun 2011)

“癌症基因组图集” (TCGA)项目组在本期Nature上报告了其对489种高等级“浆液性卵巢腺癌”中的mRNA 和 miRNA表达、启动子甲基化、DNA版本数和“外显子组”序列所做的分析。这些分析结果可帮助确定新的肿瘤亚型。该项目组的发现之一是，虽然p53肿瘤抑制因子在几乎所有肿瘤中都发生了突变，但包括NF1、BRCA1、BRCA2、 RB1和 CDK12在内的其他9个位点也携带复发性的、尽管流行度较低的突变。同源重组在约一半的这些肿瘤中是有缺陷的，Notch 和 FOXM1信号作用也牵涉到了病理生理过程中。