Integrated genomic analyses of ovarian carcinoma
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...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2012
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| Online Access: | http://hdl.handle.net/1721.1/74091 |
| _version_ | 1811069184918945792 |
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| author | Meyerson, Matthew L. Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Meyerson, Matthew L. Lander, Eric Steven |
| author_sort | Meyerson, Matthew L. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:07:03Z |
| format | Article |
| id | mit-1721.1/74091 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:07:03Z |
| publishDate | 2012 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/740912022-09-23T11:00:01Z Integrated genomic analyses of ovarian carcinoma Meyerson, Matthew L. Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric S. Meyerson, Matthew L. 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. National Institutes of Health (U.S.) (Grant U54HG003067) National Institutes of Health (U.S.) (Grant U54HG003273) National Institutes of Health (U.S.) (Grant U54HG003079) National Institutes of Health (U.S.) (Grant U24CA126543) National Institutes of Health (U.S.) (Grant U24CA126544) National Institutes of Health (U.S.) (Grant U24CA126546) National Institutes of Health (U.S.) (Grant U24CA126551) National Institutes of Health (U.S.) (Grant U24CA126554) National Institutes of Health (U.S.) (Grant U24CA126561) National Institutes of Health (U.S.) (Grant U24CA126563) National Institutes of Health (U.S.) (Grant U24CA143882) National Institutes of Health (U.S.) (Grant U24CA143731) National Institutes of Health (U.S.) (Grant U24CA143835) National Institutes of Health (U.S.) (Grant U24CA143845) National Institutes of Health (U.S.) (Grant U24CA143858) National Institutes of Health (U.S.) (Grant U24CA144025) National Institutes of Health (U.S.) (Grant U24CA143866) National Institutes of Health (U.S.) (Grant U24CA143867) National Institutes of Health (U.S.) (Grant U24CA143848) National Institutes of Health (U.S.) (Grant U24CA143843) National Institutes of Health (U.S.) (Grant R21CA135877) 2012-10-18T18:03:17Z 2012-10-18T18:03:17Z 2011-06 2010-09 Article http://purl.org/eprint/type/JournalArticle 1476-4687 0028-0836 http://hdl.handle.net/1721.1/74091 Bell, D. et al. “Integrated Genomic Analyses of Ovarian Carcinoma.” Nature 474.7353 (2011): 609–615. Web. en_US http://dx.doi.org/10.1038/nature10166 Nature Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Meyerson, Matthew L. Lander, Eric Steven Integrated genomic analyses of ovarian carcinoma |
| title | Integrated genomic analyses of ovarian carcinoma |
| title_full | Integrated genomic analyses of ovarian carcinoma |
| title_fullStr | Integrated genomic analyses of ovarian carcinoma |
| title_full_unstemmed | Integrated genomic analyses of ovarian carcinoma |
| title_short | Integrated genomic analyses of ovarian carcinoma |
| title_sort | integrated genomic analyses of ovarian carcinoma |
| url | http://hdl.handle.net/1721.1/74091 |
| work_keys_str_mv | AT meyersonmatthewl integratedgenomicanalysesofovariancarcinoma AT landerericsteven integratedgenomicanalysesofovariancarcinoma |