Integrated genomic analyses of ovarian carcinoma Journal Article
| Author: | The Cancer Genome Atlas Research Network |
| Contributors: | Dao, F.; Olvera, N.; Orsulic, S.; Park, K.; Levine, D. A.; Socci, N. D.; Liang, Y.; Taylor, B. S.; Schultz, N.; Borsu, L.; Lash, A. E.; Brennan, C.; Viale, A.; Ladanyi, M.; Sander, C.; Cerami, E.; Olshen, A.; Reva, B.; Antipin, Y.; Shen, R.; Mankoo, P.; Sheridan, R.; Ciriello, G.; Chang, W. K.; Bernanke, J. A. |
| Article Title: | Integrated genomic analyses of ovarian carcinoma |
| Abstract: | 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. © 2011 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | signal transduction; cancer survival; controlled study; human tissue; aged; middle aged; unclassified drug; gene mutation; major clinical study; somatic mutation; mutation; genetic analysis; ovarian neoplasms; microrna; gene expression; gene expression profiling; protein; brca1 protein; brca2 protein; protein p53; dna methylation; physiology; chromosome aberration; gene expression regulation, neoplastic; rna, messenger; carcinoma; ovary carcinoma; molecular analysis; genomics; genome; gene dosage; micrornas; tumor; retinoblastoma protein; disease treatment; mitochondrial dna; recombination; reproductive health; csmd3 protein; cyclin dependent kinase 12 protein; einsteinium; fat 3 protein; gamma aminobutyric acid receptor receptor 6; nuclear factor i; transcription factor foxm1 protein; pathogen |
| Journal Title: | Nature |
| Volume: | 474 |
| Issue: | 7353 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-06-30 |
| Start Page: | 609 |
| End Page: | 615 |
| Language: | English |
| DOI: | 10.1038/nature10166 |
| PUBMED: | 21720365 |
| PROVIDER: | scopus |
| PMCID: | PMC3163504 |
| DOI/URL: | |
| Notes: | - "Export Date: 17 August 2011" - "Source: Scopus" |
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