ArticleProceedings of the National Academy of Sciences of the United States of America2019
Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Summary ofGenes · 2020Pooled it
- Whole-Exome Sequencing Identifies Candidate Genomic Features Associated with Response to Platinum-Based Chemotherapy and Ixabepilone-Based Treatment in Ovarian Cancer.International journal of molecular sciences · 2026Article
- Overcoming Therapy Resistance in Ovarian Cancer: From Molecular Mechanisms to Emerging Therapeutic Strategies.Cancers · 2026Review
- Molecular Basis of Adenomatous Gastrointestinal Polyposis Syndromes: Role of Pathogenic and Benign Variants in Disease Onset.Biomedicines · 2026Article
- Mesothelial cells promote peritoneal invasion and metastasis of ascites-derived ovarian cancer cells through spheroid formation.Science advances · 2026Article
- Functional validation of somatic variability inCancer biology & therapy · 2025Article
- Article
- Immune modulation in solid tumors: a phase 1b study of RO6870810 (BET inhibitor) and atezolizumab (PD-L1 inhibitor).BMC cancer · 2025Article
- Harnessing transcriptional regulation of alternative end-joining to predict cancer treatment.NAR cancer · 2025Article
- Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome- paving the path towards precision medicine: a case report.Journal of cancer research and clinical oncology · 2025Article
- Utility of next generation sequencing to unequivocally establish clonality in synchronous vs metastatic endometrial and ovarian carcinomas.Gynecologic oncology reports · 2024Article
- Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2.Clinical & experimental metastasis · 2024Article
- Integrated analysis of spatial transcriptomics and CT phenotypes for unveiling the novel molecular characteristics of recurrent and non-recurrent high-grade serous ovarian cancer.Biomarker research · 2024Article
- Article
- Ovarian carcinosarcoma is highly aggressive compared to other ovarian cancer histotypes.Frontiers in oncology · 2024Article
- Clinicopathological and molecular features of tubo-ovarian carcinosarcomas: a series of 51 cases.Frontiers in oncology · 2024Article
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- Advances in application of circulating tumor DNA in ovarian cancer.Functional & integrative genomics · 2023Review
- Genomic analyses of germline and somatic variation in high-grade serous ovarian cancer.Journal of ovarian research · 2023Article
- In silico enhancer mining reveals SNS-032 and EHMT2 inhibitors as therapeutic candidates in high-grade serous ovarian cancer.British journal of cancer · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
39 authors at 2 institutions in 2 countries.
Funding
Abstract
Ovarian cancer remains the most lethal gynecologic malignancy. We analyzed the mutational landscape of 64 primary, 41 metastatic, and 17 recurrent fresh-frozen tumors from 77 patients along with matched normal DNA, by whole-exome sequencing (WES). We also sequenced 13 pairs of synchronous bilateral ovarian cancer (SBOC) to evaluate the evolutionary history. Lastly, to search for therapeutic targets, we evaluated the activity of the Bromodomain and Extra-Terminal motif (BET) inhibitor GS-626510 on primary tumors and xenografts harboring c-MYC amplifications. In line with previous studies, the large majority of germline and somatic mutations were found in BRCA1/2 (21%) and TP53 (86%) genes, respectively. Among mutations in known cancer driver genes, 77% were transmitted from primary tumors to metastatic tumors, and 80% from primary to recurrent tumors, indicating that driver mutations are commonly retained during ovarian cancer evolution. Importantly, the number, mutation spectra, and signatures in matched primary-metastatic tumors were extremely similar, suggesting transcoelomic metastases as an early dissemination process using preexisting metastatic ability rather than an evolution model. Similarly, comparison of SBOC showed extensive sharing of somatic mutations, unequivocally indicating a common ancestry in all cases. Among the 17 patients with matched tumors, four patients gained PIK3CA amplifications and two patients gained c-MYC amplifications in the recurrent tumors, with no loss of amplification or gain of deletions. Primary cell lines and xenografts derived from chemotherapy-resistant tumors demonstrated sensitivity to JQ1 and GS-626510 (
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