ArticleNucleic acids research2015
TP53 mutations, tetraploidy and homologous recombination repair defects in early stage high-grade serous ovarian cancer.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Morphological and molecular characterization of epithelial ovarian cancer: SEOM-SEAP consensus guidelines for biomarker integration in clinical practice.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Guideline
- Integrated Single-Cell Whole-Genome Sequencing and Spatial Transcriptomics Reveal Intratumoral Heterogeneity in Ovarian Cancer.Cancer research communications · 2026Article
- Mesothelial cells promote peritoneal invasion and metastasis of ascites-derived ovarian cancer cells through spheroid formation.Science advances · 2026Article
- Recurrence Patterns After Complete Cytoreduction for Advanced Ovarian Cancer: Robotic Versus Open Surgery.Current oncology (Toronto, Ont.) · 2026Article
- Replication stress and defective checkpoints make fallopian tube epithelial cells putative drivers of high-grade serous ovarian cancer.Cell reports · 2023Article
- The Current Status of DNA-Repair-Directed Precision Oncology Strategies in Epithelial Ovarian Cancers.International journal of molecular sciences · 2023Review
- Characterization of BRCA Deficiency in Ovarian Cancer.Cancers · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- Molecular Management of High-Grade Serous Ovarian Carcinoma.International journal of molecular sciences · 2022Review
- The Genomic Landscape of Early-Stage Ovarian High-Grade Serous Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer, Part 1: Technical Considerations.Cancers · 2022Review
- Race-Specific Genetic Profiles of Homologous Recombination Deficiency in Multiple Cancers.Journal of personalized medicine · 2021Article
- Genomic alterations in gynecological malignancies: histotype-associated driver mutations, molecular subtyping schemes, and tumorigenic mechanisms.Journal of human genetics · 2021Review
- Mechanisms of High-Grade Serous Carcinogenesis in the Fallopian Tube and Ovary: Current Hypotheses, Etiologic Factors, and Molecular Alterations.International journal of molecular sciences · 2021Review
- Clinical relevance of TP53 hotspot mutations in high-grade serous ovarian cancers.British journal of cancer · 2020Article
- Bioinformatics and functional analyses of key genes in smoking-associated lung adenocarcinoma.Oncology letters · 2019Article
- Ultra-Sensitive TP53 Sequencing for Cancer Detection Reveals Progressive Clonal Selection in Normal Tissue over a Century of Human Lifespan.Cell reports · 2019Article
- Exploiting DNA repair defects in colorectal cancer.Molecular oncology · 2019Review
- Interferon-γ signaling is associated withNPJ precision oncology · 2019Article
- An In-Depth Look at Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT): Clinical Implications from Recent Molecular Findings.Journal of Cancer · 2019Review
Corrections and comments
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Authors and funding
30 authors at 10 institutions in 2 countries.
Funding
Abstract
To determine early somatic changes in high-grade serous ovarian cancer (HGSOC), we performed whole genome sequencing on a rare collection of 16 low stage HGSOCs. The majority showed extensive structural alterations (one had an ultramutated profile), exhibited high levels of p53 immunoreactivity, and harboured a TP53 mutation, deletion or inactivation. BRCA1 and BRCA2 mutations were observed in two tumors, with nine showing evidence of a homologous recombination (HR) defect. Combined Analysis with The Cancer Genome Atlas (TCGA) indicated that low and late stage HGSOCs have similar mutation and copy number profiles. We also found evidence that deleterious TP53 mutations are the earliest events, followed by deletions or loss of heterozygosity (LOH) of chromosomes carrying TP53, BRCA1 or BRCA2. Inactivation of HR appears to be an early event, as 62.5% of tumours showed a LOH pattern suggestive of HR defects. Three tumours with the highest ploidy had little genome-wide LOH, yet one of these had a homozygous somatic frame-shift BRCA2 mutation, suggesting that some carcinomas begin as tetraploid then descend into diploidy accompanied by genome-wide LOH. Lastly, we found evidence that structural variants (SV) cluster in HGSOC, but are absent in one ultramutated tumor, providing insights into the pathogenesis of low stage HGSOC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.