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
Notes: - "Export Date: 17 August 2011" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Douglas A Levine
    356 Levine
  2. Ronglai Shen
    127 Shen
  3. Cameron Brennan
    155 Brennan
  4. Marc Ladanyi
    870 Ladanyi
  5. Kay Jung Park
    182 Park
  6. Adam B Olshen
    107 Olshen
  7. Agnes Viale
    205 Viale
  8. Boris A Reva
    36 Reva
  9. Alex E Lash
    24 Lash
  10. Parminder Kaur Mankoo
    3 Mankoo
  11. Narciso Olvera
    71 Olvera
  12. Nicholas D Socci
    186 Socci
  13. Chris Sander
    196 Sander
  14. Fanny Dao
    56 Dao
  15. Barry Stephen Taylor
    141 Taylor
  16. Ethan Cerami
    21 Cerami
  17. Nikolaus D Schultz
    202 Schultz
  18. Yevgeniy Antipin
    19 Antipin
  19. Yupu Liang
    8 Liang
  20. William K Chang
    3 Chang