Cited by 236Ovarian cancer diagnosis and treatmentBRCA gene mutations in cancerChromatin Remodeling and Cancer

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Integrated genomic analyses of ovarian carcinoma

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The Cancer Genome Atlas Research Network·2011·Nature

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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. The Cancer Genome Atlas (TCGA) project reports here its analysis of messenger RNA and microRNA expression, promoter methylation, DNA copy number and exome sequences in 489 high-grade serous ovarian adenocarcinomas. The analyses help establish new tumour subtypes. Among other insights is the finding that while the gene encoding p53 tumour suppressor is mutated in almost all tumours, nine other loci including NF1, BRCA1, BRCA2, RB1 and CDK12 carry recurrent albeit low-prevalence mutations. Homologous recombination is defective in about half of the tumours studied, and Notch and FOXM1 signalling are involved in the pathophysiology.

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Authors: The Cancer Genome Atlas Research Network
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2011-06-29
Volume: 474
Issue: 7353
Pages: 609-615
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature10166
PMC: PMC3163504
OpenAlex: W2216554257
Cited by: 129
References: 50
Citations by year: 2026: 51 · 2025: 2 · 2024: 14 · 2023: 8 · 2022: 9 · 2021: 13 · 2020: 10 · 2019: 5 · 2018: 4 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 2
FWCI: 2.51
Type: journal article
Language: en
Update notices: erratum (2012-08-22)
Open access: hybrid
doi.org
Licence: other-oa
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion, other-oa)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
Spiral (Imperial College London) (submittedVersion)
Padua Research Archive (University of Padova) (submittedVersion, other-oa)
UNC Libraries
Funders: National Institutes of Health
National Human Genome Research Institute (U54HG003067, U54HG003079, U54HG003273, R01HG005690)
National Cancer Institute (R01CA094143, R21CA135877, U24CA126554, U24CA143882, R01CA140323, U24CA143843, U24CA143840, U24CA126546, U24CA143858, U24CA126543, U24CA144025, U24CA126563, U24CA143866, U24CA143845, U24CA126544, U24CA143867, U24CA143848, U24CA126551, U24CA143835, U24CA126561, P50CA136393)
National Institute of Dental and Craniofacial Research (R21DE019713)
Topics: Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: TP53 mutation, somatic mutations, BRCA1, BRCA2, neurofibromatosis type 1, RB1, CDK12, DNA copy number aberrations, promoter methylation, microRNA expression, mRNA expression, transcriptomic subtypes, homologous recombination deficiency, Notch signaling, cyclin E1, survival, tumor subtypes
MeSH terms: Aged, Carcinoma, Female, Humans, Middle Aged, Mutation, Ovarian Neoplasms, RNA, Messenger, Gene Expression Regulation, Neoplastic, Gene Dosage, DNA Methylation, Gene Expression Profiling, Genomics, MicroRNAs

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