Integrated genomic analyses of ovarian carcinoma
- PMID: 21720365
- PMCID: PMC3163504
- DOI: 10.1038/nature10166
Integrated genomic analyses of ovarian carcinoma
Erratum in
- Nature. 2012 Oct 11;490(7419):298
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.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3163504/bin/nihms-313090-f0001.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3163504/bin/nihms-313090-f0002.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3163504/bin/nihms-313090-f0003.gif)
Similar articles
-
Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations.Clin Cancer Res. 2013 Jul 1;19(13):3474-84. doi: 10.1158/1078-0432.CCR-13-0066. Epub 2013 Apr 30. Clin Cancer Res. 2013. PMID: 23633455
-
Comprehensive molecular portraits of human breast tumours.Nature. 2012 Oct 4;490(7418):61-70. doi: 10.1038/nature11412. Epub 2012 Sep 23. Nature. 2012. PMID: 23000897 Free PMC article.
-
BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma.Mod Pathol. 2012 May;25(5):740-50. doi: 10.1038/modpathol.2011.211. Epub 2012 Jan 27. Mod Pathol. 2012. PMID: 22282309
-
The genesis and evolution of high-grade serous ovarian cancer.Nat Rev Cancer. 2010 Nov;10(11):803-8. doi: 10.1038/nrc2946. Epub 2010 Oct 14. Nat Rev Cancer. 2010. PMID: 20944665 Review.
-
Targeting DNA repair: the genome as a potential biomarker.J Pathol. 2018 Apr;244(5):586-597. doi: 10.1002/path.5025. Epub 2018 Feb 10. J Pathol. 2018. PMID: 29282716 Review.
Cited by
-
The Progression and Prospects of the Gene Expression Profiling in Ovarian Epithelial Cancer.Gynecol Minim Invasive Ther. 2024 Jul 18;13(3):141-145. doi: 10.4103/gmit.gmit_13_23. eCollection 2024 Jul-Sep. Gynecol Minim Invasive Ther. 2024. PMID: 39184260 Free PMC article. Review.
-
Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review.Open Med (Wars). 2024 Aug 20;19(1):20249999. doi: 10.1515/med-2024-9999. eCollection 2024. Open Med (Wars). 2024. PMID: 39176249 Free PMC article.
-
Application of PARP inhibitors combined with immune checkpoint inhibitors in ovarian cancer.J Transl Med. 2024 Aug 21;22(1):778. doi: 10.1186/s12967-024-05583-z. J Transl Med. 2024. PMID: 39169400 Free PMC article. Review.
-
MicroRNA-486-3p affects cisplatin resistance in high-grade serous ovarian cancer by regulating TMIGD2: An experimental study.Heliyon. 2024 Jul 19;10(15):e34978. doi: 10.1016/j.heliyon.2024.e34978. eCollection 2024 Aug 15. Heliyon. 2024. PMID: 39145009 Free PMC article.
-
Integrated genomic/epigenomic analysis stratifies subtypes of clear cell ovarian carcinoma, highlighting their cellular origin.Sci Rep. 2024 Aug 13;14(1):18797. doi: 10.1038/s41598-024-69796-4. Sci Rep. 2024. PMID: 39138354 Free PMC article.
References
-
- Jemal A, Siegel R, Xu J, Ward E. Cancer Statistics, 2010. CA Cancer J Clin - PubMed
-
- Koonings PP, Campbell K, Mishell DR, Jr., Grimes DA. Relative frequency of primary ovarian neoplasms: a 10-year review. Obstet Gynecol. 1989;74:921–926. - PubMed
-
- Seidman JD, et al. The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin. Int J Gynecol Pathol. 2004;23:41–44. - PubMed
-
- Jemal A, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–249. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- U24 CA143882/CA/NCI NIH HHS/United States
- U24CA143731/CA/NCI NIH HHS/United States
- U24CA126551/CA/NCI NIH HHS/United States
- U24CA144025/CA/NCI NIH HHS/United States
- U54 HG003273/HG/NHGRI NIH HHS/United States
- R01 HG005690/HG/NHGRI NIH HHS/United States
- U24 CA144025/CA/NCI NIH HHS/United States
- U24 CA143843/CA/NCI NIH HHS/United States
- U24CA143867/CA/NCI NIH HHS/United States
- U24 CA143867/CA/NCI NIH HHS/United States
- U24CA143840/CA/NCI NIH HHS/United States
- R21 DE019713/DE/NIDCR NIH HHS/United States
- R01 CA140323/CA/NCI NIH HHS/United States
- U24CA126561/CA/NCI NIH HHS/United States
- U54 HG003067/HG/NHGRI NIH HHS/United States
- U54HG003273/HG/NHGRI NIH HHS/United States
- U24 CA143835/CA/NCI NIH HHS/United States
- U24CA126543/CA/NCI NIH HHS/United States
- U24CA126554/CA/NCI NIH HHS/United States
- R01 CA094143/CA/NCI NIH HHS/United States
- U24 CA143866/CA/NCI NIH HHS/United States
- U24CA143858/CA/NCI NIH HHS/United States
- U24CA126544/CA/NCI NIH HHS/United States
- U24CA143882/CA/NCI NIH HHS/United States
- U24 CA126551/CA/NCI NIH HHS/United States
- U54HG003067/HG/NHGRI NIH HHS/United States
- R21 CA135877/CA/NCI NIH HHS/United States
- U24 CA143845/CA/NCI NIH HHS/United States
- U54HG003079/HG/NHGRI NIH HHS/United States
- U24 CA126554/CA/NCI NIH HHS/United States
- U24 CA143840/CA/NCI NIH HHS/United States
- U24CA143835/CA/NCI NIH HHS/United States
- U24 CA126561/CA/NCI NIH HHS/United States
- U24 CA143858/CA/NCI NIH HHS/United States
- U24CA143843/CA/NCI NIH HHS/United States
- U24 CA143848/CA/NCI NIH HHS/United States
- U24 CA126543/CA/NCI NIH HHS/United States
- U24CA143848/CA/NCI NIH HHS/United States
- U24CA126563/CA/NCI NIH HHS/United States
- U24CA126546/CA/NCI NIH HHS/United States
- U54 HG003079/HG/NHGRI NIH HHS/United States
- R21 CA135877-01/CA/NCI NIH HHS/United States
- R21 CA135877-02/CA/NCI NIH HHS/United States
- U24CA143866/CA/NCI NIH HHS/United States
- U24CA143845/CA/NCI NIH HHS/United States
- U24 CA126546/CA/NCI NIH HHS/United States
- P50 CA136393/CA/NCI NIH HHS/United States
- U24 CA126563/CA/NCI NIH HHS/United States
- U24 CA126544/CA/NCI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous