Genetics of Ovarian Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 2884

Special Issue Editors


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Guest Editor
1. Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK
2. Medway NHS Foundation Trust, Windmill Road, Gillingham ME7 5NY, Kent, UK
3. Kent Medway Medical School, University of Kent, Canterbury CT2 7LX, Kent, UK
4. AELIA Organization, 9(th)Km Thessaloniki-Thermi, 57001 Thessaloniki, Greece
Interests: prostate cancer; renal cancer; ovarian cancer; homologous recombination of DNA; PARP inhibitors; cervical cancer; carcinoma of unknown primary; colorectal cancer; cancer and autoimmune diseases; biomarkers
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E-Mail Website
Guest Editor
1. High Dimensional Neurology Group, UCL Queen's Square Institute of Neurology, London WC1N 3BG, UK
2. 10Department of Oncology, Guy's and St Thomas' Hospital, London SE1 9RT, UK
3. School of Cancer & Pharmaceutical Sciences, King's College London, Strand, London WC2R 2LS, UK
Interests: novel MRI techniques; ovarian cancer;prostate cancer

Special Issue Information

Dear Colleagues,

Epithelial ovarian cancers (EOC), characterised by recurrent, persistent disease and the rapid acquisition of chemotherapy resistance, remain one of the most lethal gynaecological malignancies. DNA damage is one of the hallmarks of cancer. Among EOC, the high-grade serous subtype harbours a defect in at least one DNA damage response (DDR) pathway. Defective DDR results from a variety of lesions affecting homologous recombination (HR) and nonhomologous end joining (NHEJ) for double strand breaks, base excision repair (BER), and nucleotide excision repair (NER) for single strand breaks and mismatch repair (MMR).

We are pleased to invite you to submit your manuscripts and help the community to understand that DDR pathways are essential in order to optimize the therapeutic choices, as well as highlight the importance of designing biomarker-driven clinical trials. Poly(ADP-ribose) polymerase (PARP) inhibitors are a well-established treatment of EOC. Moreover, combinations of PARP inhibitors with drugs that inhibit HR may sensitise EOC with a primary or secondary HR proficiency to PARP inhibitors and potentially expand their use beyond HR-deficient ovarian cancers. Regarding this, PARP inhibitors may be combined separately with anti-angiogenics and immune checkpoint inhibitors as well as with phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), WEE1, mitogen-activated protein kinase (MEK), and cyclin-dependent kinase (CDK) 4/6 inhibitors, or even with standard chemotherapy.

Through this Special Issue, we aim to shed light on the mechanisms of DDR, the potential for genomic analysis of ovarian cancer, and therapeutics of PARP inhibitors, along with predictive biomarkers.

This Special Issue welcomes manuscripts that include, though it is not limited to, the following topics:

  • EOC risk assessment in the era of next-generation sequencing;
  • Predictive and prognostic biomarkers in EOC;
  • DNA damage response;
  • PARP inhibitors in EOC;
  • PARP inhibitors in combination with other therapies;
  • Immunotherapy in EOC;
  • Chemoresistance;
  • Regression;
  • Invasion.

We look forward to receiving your contributions.

Dr. Stergios Boussios
Dr. Sola Adeleke
Guest Editors

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Keywords

  • epithelial ovarian cancer
  • genomics
  • epigenetics
  • translational research
  • biomarkers
  • DNA damage response
  • PARP inhibitors

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Published Papers (2 papers)

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Research

15 pages, 2596 KiB  
Article
The Prognostic Role of BRD4 Expression in High-Grade Serous Ovarian Cancer
by Angeliki Andrikopoulou, Garyfalia Bletsa, Angeliki Rouvalis, Dimitris Tsakogiannis, Maria Kaparelou, Alkistis Papatheodoridi, Dimitrios Haidopoulos, Michalis Liontos, Meletios-Athanasios Dimopoulos and Flora Zagouri
Cancers 2024, 16(11), 1962; https://doi.org/10.3390/cancers16111962 - 22 May 2024
Viewed by 963
Abstract
Background: Bromodomain and extra-terminal (BET) domain proteins that bind to acetylated lysine residues of histones serve as the “readers” of DNA acetylation. BRD4 is the most thoroughly studied member of the BET family and regulates the expression of key oncogenes. BRD4 gene amplification [...] Read more.
Background: Bromodomain and extra-terminal (BET) domain proteins that bind to acetylated lysine residues of histones serve as the “readers” of DNA acetylation. BRD4 is the most thoroughly studied member of the BET family and regulates the expression of key oncogenes. BRD4 gene amplification has been identified in ovarian cancer (~18–19%) according to The Cancer Genome Atlas (TCGA) analysis. BET inhibitors are novel small molecules that displace BET proteins from acetylated histones and are currently tested in Phase I/II trials. We here aim to explore the prognostic role of the BRD4 gene and protein expression in the ascitic fluid of patients with advanced FIGO III/IV high-grade serous ovarian carcinoma (HGSC). Methods: Ascitic fluid was obtained from 28 patients with advanced stage (FIGO III/IV) HGSC through diagnostic/therapeutic paracentesis or laparoscopy before the initiation of chemotherapy. An amount of ~200 mL of ascitic fluid was collected from each patient and peripheral blood mononuclear cells (PBMCs) were isolated. Each sample was evaluated for BRD4 and GAPDH gene expression through RT-qPCR and BRD4 protein levels through enzyme-linked immunosorbent assay (ELISA). The study protocol was approved by the Institutional Review Board of Alexandra University Hospital and the Committee on Ethics and Good Practice (CEGP) of the National and Kapodistrian University of Athens (NKUA). Results: Low BRD4 gene expression was associated with worse prognosis at 12 months compared to intermediate/high expression (95% CI; 1.75–30.49; p = 0.008). The same association was observed at 24 months although this association was not statistically significant (95% CI; 0.96–9.2; p = 0.065). Progression-free survival was shorter in patients with low BRD4 gene expression at 12 months (5.6 months; 95% CI; 2.6–8.6) compared to intermediate/high expression (9.8 months; 95% CI; 8.3–11.3) (95% CI; 1.2–16.5; p = 0.03). The same association was confirmed at 24 months (6.9 months vs. 13.1 months) (95% CI; 1.1–8.6; p = 0.048). There was a trend for worse prognosis in patients with high BRD4 protein levels versus intermediate/low BRD4 protein expression both at 12 months (9.8 months vs. 7.6 months; p = 0.3) and at 24 months (14.2 months vs. 16.6 months; p = 0.56) although not statistically significant. Again, there was a trend for shorter PFS in patients with high BRD4 protein expression although not statistically significant both at 12 months (p = 0.29) and at 24 months (p = 0.47). Conclusions: There are contradictory data in the literature over the prognostic role of BRD4 gene expression in solid tumors. In our study, intermediate/high BRD4 gene expression was associated with a favorable prognosis in terms of overall survival and progression-free survival compared to low BRD4 gene expression. Full article
(This article belongs to the Special Issue Genetics of Ovarian Cancer)
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19 pages, 4299 KiB  
Article
Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian Carcinoma
by Efthymia Papakonstantinou, Ioanna Pappa, Georgios Androutsopoulos, Georgios Adonakis, Ioannis Maroulis and Vasiliki Tzelepi
Cancers 2023, 15(20), 4950; https://doi.org/10.3390/cancers15204950 - 11 Oct 2023
Viewed by 1248
Abstract
Background: Despite recent advances in epithelial ovarian carcinoma (EOC) treatment, its recurrence and mortality rates have not improved significantly. DNA hypermethylation has generally been associated with an ominous prognosis and chemotherapy resistance, but the role of DNA methyltransferases (DNMTs) in EOC remains to [...] Read more.
Background: Despite recent advances in epithelial ovarian carcinoma (EOC) treatment, its recurrence and mortality rates have not improved significantly. DNA hypermethylation has generally been associated with an ominous prognosis and chemotherapy resistance, but the role of DNA methyltransferases (DNMTs) in EOC remains to be investigated. Methods: In the current study, we systematically retrieved gene expression data from patients with EOC and studied the immunohistochemical expression of DNMTs in 108 primary and 26 relapsed tumors. Results: Our results showed that the DNMT1, DNMT3A, DNMT3B and DNMT3L RNA levels were higher and the DNMT2 level was lower in tumors compared to non-neoplastic tissue, and DNMT3A and DNMT2 expression decreased from Stage-II to Stage-IV carcinomas. The proteomic data also suggested that the DNMT1 and DNMT3A levels were increased in the tumors. Similarly, the DNMT1, DNMT3A and DNMT3L protein levels were overexpressed and DNMT2 expression was reduced in high-grade carcinomas compared to non-neoplastic tissue and low-grade tumors. Moreover, DNMT1 and DNMT3L were increased in relapsed tumors compared to their primaries. The DNMT3A, DNMT1 and DNMT3B mRNA levels were correlated with overall survival. Conclusions: Our study demonstrates that DNMT1 and DNMT3L are upregulated in primary high-grade EOC and further increase in relapses, whereas DNMT3A is upregulated only in the earlier stages of cancer progression. DNMT2 downregulation highlights the presumed tumor-suppressor activity of this gene in ovarian carcinoma. Full article
(This article belongs to the Special Issue Genetics of Ovarian Cancer)
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