ArticleProceedings of the National Academy of Sciences of the United States of America2016
Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial-mesenchymal transition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 3 of them syntheses 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
143 citing papers in PubMed, 3 syntheses or guidelines pooled it, 229 citations in OpenAlex.
- Contribution of histone variants to aneuploidy: a cancer perspective.Frontiers in genetics · 2023Pooled it
- TCGA Classification of Endometrial Cancer: the Place of Carcinosarcoma.Pathology oncology research : POR · 2020Pooled it
- Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives.International journal of molecular sciences · 2017Pooled it
- Trial
- A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793).Annals of oncology : official journal of the European Society for Medical Oncology · 2021Trial
- A High-Fidelity and Ancestrally Inclusive Patient-Derived Organoid Platform Resolves Cancer Cell Plasticity in Uterine Carcinosarcoma.bioRxiv : the preprint server for biology · 2026Article
- Ovarian Carcinosarcoma With Heterologous Chondrosarcomatous Differentiation: A Case Report and Review of Literature.Cureus · 2026Article
- Is cancer the result of uncontrolled cellular growth? a glance into the tumorigenic process.Cancer cell international · 2026Review
- High-throughput drug screening identifies EGFR/MAPK pathway targeting sensitivities in organoid models of ovarian carcinosarcoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Synchronous Ovarian and Cervical Malignancies: A Case Report of Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery and Niraparib Maintenance.International journal of women's health · 2026Article
- Endometriosis-Associated Ovarian Carcinosarcoma Featuring Well-Differentiated Adenocarcinoma and Fetal Rhabdomyoma-Like Mesenchymal Components: An Unusual Case Report-With Molecular Analysis.Case reports in pathology · 2026Article
- Targeting Ovarian Neoplasms: Subtypes and Therapeutic Options.Medicina (Kaunas, Lithuania) · 2025Review
- Role of long non-coding RNA-mRNA interactions in resveratrol-mediated inhibition of ovarian cancer cell proliferation.Oncology letters · 2025Article
- Natural and induced epithelial-mesenchymal transition results in epigenetic silencing of HER2 overexpression.Journal of mammary gland biology and neoplasia · 2025Article
- Dissecting the histological heterogeneity of ovarian carcinosarcoma and high-grade serous ovarian cancer in primary and metastatic tumors by single-cell transcriptomic analysis.Chinese medical journal · 2025Article
- Clinicopathological Predictors of Recurrence in Uterine Sarcomas-A Narrative Review.Journal of clinical medicine · 2025Review
- Carcinosarcoma of the Endometrium-Pathology, Molecular Landscape and Novel Therapeutic Approaches.Medicina (Kaunas, Lithuania) · 2025Review
- Loss of SMARCA4 induces sarcomatogenesis through epithelial-mesenchymal transition in ovarian carcinosarcoma.Cancer science · 2025Article
- Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer.Cancer research · 2025Article
- Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.Experimental hematology & oncology · 2025Review
83 more citing papers are in PubMed but not listed here.
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Authors and funding
47 authors at 7 institutions in 3 countries.
Funding
Abstract
Carcinosarcomas (CSs) of the uterus and ovary are highly aggressive neoplasms containing both carcinomatous and sarcomatous elements. We analyzed the mutational landscape of 68 uterine and ovarian CSs by whole-exome sequencing. We also performed multiregion whole-exome sequencing comprising two carcinoma and sarcoma samples from six tumors to resolve their evolutionary histories. The results demonstrated that carcinomatous and sarcomatous elements derive from a common precursor having mutations typical of carcinomas. In addition to mutations in cancer genes previously identified in uterine and ovarian carcinomas such as TP53, PIK3CA, PPP2R1A, KRAS, PTEN, CHD4, and BCOR, we found an excess of mutations in genes encoding histone H2A and H2B, as well as significant amplification of the segment of chromosome 6p harboring the histone gene cluster containing these genes. We also found frequent deletions of the genes TP53 and MBD3 (a member with CHD4 of the nucleosome remodeling deacetylase complex) and frequent amplification of chromosome segments containing the genes PIK3CA, TERT, and MYC Stable transgenic expression of H2A and H2B in a uterine serous carcinoma cell line demonstrated that mutant, but not wild-type, histones increased expression of markers of epithelial-mesenchymal transition (EMT) as well as tumor migratory and invasive properties, suggesting a role in sarcomatous transformation. Comparison of the phylogenetic relationships of carcinomatous and sarcomatous elements of the same tumors demonstrated separate lineages leading to these two components. These findings define the genetic landscape of CSs and suggest therapeutic targets for these highly aggressive neoplasms.
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Registered trials
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.