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Journals / Black Sea Journal of Health Science / 2026 / Cilt: 9 Sayı: 1

Poly (ADP-ribose) Polymerase Inhibitor Responses in High-Grade Serous Ovarian Cancer: Insights from BRCA Germline-Negative and Somatic Mutation-Positive Cases

Metin Eser(UNIVERSITY OF HEALTH SCIENCES, İSTANBUL ÜMRANİYE HEALTH RESEARCH CENTER, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL GENETICS)0000-0001-7118-7958
Gulam Hekimoğlu(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, HAMİDİYE ULUSLARARASI TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, HİSTOLOJİ VE EMBRİYOLOJİ ANABİLİM DALI)0000-0002-5027-6756
Murat Hakkı Yarar(UNIVERSITY OF HEALTH SCIENCES, İSTANBUL ÜMRANİYE HEALTH RESEARCH CENTER, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL GENETICS)0000-0001-8481-9803
Fatma Gülçiçek Ayrancı(UNIVERSITY OF HEALTH SCIENCES, İSTANBUL ÜMRANİYE HEALTH RESEARCH CENTER, DEPARTMENT OF SURGICAL MEDICAL SCIENCES, DEPARTMENT OF MEDICAL PATHOLOGY)0000-0001-6217-4899
Esra Keles Peker(UNIVERSITY OF HEALTH SCIENCES, İSTANBUL KARTAL DR. LÜTFİ KIRDAR HEALTH RESEARCH CENTER, DEPARTMENT OF SURGICAL MEDICAL SCIENCES, DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY, GYNECOLOGICAL ONCOLOGY)0000-0001-8099-8883
Murat Api(UNIVERSITY OF HEALTH SCIENCES, İSTANBUL KARTAL DR. LÜTFİ KIRDAR HEALTH RESEARCH CENTER, DEPARTMENT OF SURGICAL MEDICAL SCIENCES, DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY)0000-0001-9442-2690
Melike Özçelik(UNIVERSITY OF HEALTH SCIENCES, İSTANBUL ÜMRANİYE HEALTH RESEARCH CENTER, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, ONCOLOGY)0000-0003-0406-715X
Pages
18–24
Publication Date
2025-12-24
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

As treatments evolve, integrating comprehensive genetic testing into clinical practice is vital to improving care.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:High-grade serous ovarian cancer (HGSOC) is an aggressive form of epithelial carcinoma associated with poor prognosis.
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Key Findings & Data:Although relatively uncommon, mutations in the BRCA1/2 genes are linked to HGSOC.
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Conclusion & Impact:As treatments evolve, integrating comprehensive genetic testing into clinical practice is vital to improving care.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:BRCA1/2 · High-grade serous ovarian cancer · PARPi

Abstract

High-grade serous ovarian cancer (HGSOC) is an aggressive form of epithelial carcinoma associated with poor prognosis. Although relatively uncommon, mutations in the BRCA1/2 genes are linked to HGSOC. Poly(ADP-ribose) polymerase inhibitors (PARPi) have been approved for treating patients with BRCA1/2 mutations, significantly improving outcomes for this subgroup. To assess the prevalence of BRCA1/2 mutations in high-grade serous ovarian cancer (HGSOC) patients who tested negative for germline BRCA1/2 mutations and to evaluate the potential implications of tumor-based genetic testing for expanding PARPi therapy eligibility. 75 patients who underwent Somatic BRCA1/BRCA2 Next Generation Sequencing (NGS) and were positive for somatic but negative for germline BRCA1/2 mutations were selected and included in the study. Tumor tissue samples, either formalin-fixed paraffin-embedded or fresh, were analyzed using NGS to detect somatic mutations in BRCA1/2 genes. The study also examined variants of uncertain significance (VUS) within these genes. Pathogenic somatic mutations in the BRCA1/2 genes were identified in 8 patients (11%), while a VUS was detected in 1 patient (1%). Variant mutations c.135-8A>G, c.1084G>T (p.Glu362Ter), c.5095C>T (p.Arg1699Trp), and c.3756_3759del (p.Ser1253fs) were found in the BRCA1 gene, while c.5073dup (p.Trp1692fs), c.426-1G>A, c.3751_3752insA (p.Thr1251AsnfsTer14), and c.771_775del (p.Asn257fs) were found in the BRCA2 gene. Our study highlights the importance of expanding the availability of PARPi therapy to patients with somatic BRCA1/2 mutations and providing targeted therapy to guide patients with high-grade ovarian serous cancer. As treatments evolve, integrating comprehensive genetic testing into clinical practice is vital to improving care.

Özet

High-grade serous ovarian cancer (HGSOC) is an aggressive form of epithelial carcinoma associated with poor prognosis. Although relatively uncommon, mutations in the BRCA1/2 genes are linked to HGSOC. Poly(ADP-ribose) polymerase inhibitors (PARPi) have been approved for treating patients with BRCA1/2 mutations, significantly improving outcomes for this subgroup. To assess the prevalence of BRCA1/2 mutations in high-grade serous ovarian cancer (HGSOC) patients who tested negative for germline BRCA1/2 mutations and to evaluate the potential implications of tumor-based genetic testing for expanding PARPi therapy eligibility. 75 patients who underwent Somatic BRCA1/BRCA2 Next Generation Sequencing (NGS) and were positive for somatic but negative for germline BRCA1/2 mutations were selected and included in the study. Tumor tissue samples, either formalin-fixed paraffin-embedded or fresh, were analyzed using NGS to detect somatic mutations in BRCA1/2 genes. The study also examined variants of uncertain significance (VUS) within these genes. Pathogenic somatic mutations in the BRCA1/2 genes were identified in 8 patients (11%), while a VUS was detected in 1 patient (1%). Variant mutations c.135-8A>G, c.1084G>T (p.Glu362Ter), c.5095C>T (p.Arg1699Trp), and c.3756_3759del (p.Ser1253fs) were found in the BRCA1 gene, while c.5073dup (p.Trp1692fs), c.426-1G>A, c.3751_3752insA (p.Thr1251AsnfsTer14), and c.771_775del (p.Asn257fs) were found in the BRCA2 gene. Our study highlights the importance of expanding the availability of PARPi therapy to patients with somatic BRCA1/2 mutations and providing targeted therapy to guide patients with high-grade ovarian serous cancer. As treatments evolve, integrating comprehensive genetic testing into clinical practice is vital to improving care.

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Cite This Article

Eser, M., Hekimoğlu, G., Yarar, M. H., Ayrancı, F. G., Peker, E. K., Api, M., Özçelik, M. (2025). Poly (ADP-ribose) Polymerase Inhibitor Responses in High-Grade Serous Ovarian Cancer: Insights from BRCA Germline-Negative and Somatic Mutation-Positive Cases. Black Sea Journal of Health Science, Cilt: 9 Sayı: 1, 18–24. https://doi.org/10.19127/bshealthscience.1793827

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