Case Report: Clinical impact of BRCA1 and BRIP1 vs. BRCA1 and BRCA2 germline double heterozygosity in ovarian cancer: a comparative case study
Ovarian cancer (OC) is a highly heterogeneous malignancy influenced by germline genetic factors, with BRCA1/2 mutations being well-established risk factors. Germline double heterozygosity (GDH), particularly involving rare combinations, remains poorly understood. This study presents the first report...
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| Format: | Article |
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1614373/full |
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| author | Limei Zheng Qianyuan Zhu Qianyuan Zhu Fenglan Zhang Hao Qiu Lan Qin Jianhua Yang Ming Qi Ming Qi Ming Qi Ming Qi |
| author_facet | Limei Zheng Qianyuan Zhu Qianyuan Zhu Fenglan Zhang Hao Qiu Lan Qin Jianhua Yang Ming Qi Ming Qi Ming Qi Ming Qi |
| author_sort | Limei Zheng |
| collection | DOAJ |
| description | Ovarian cancer (OC) is a highly heterogeneous malignancy influenced by germline genetic factors, with BRCA1/2 mutations being well-established risk factors. Germline double heterozygosity (GDH), particularly involving rare combinations, remains poorly understood. This study presents the first report of BRCA1/BRIP1 GDH in a case of Chinese OC patients and compares their clinical characteristics and treatment responses to a patient with BRCA1/BRCA2 GDH. The BRCA1/BRIP1 GDH patient is a 46-year-old female diagnosed with advanced ovarian adenocarcinoma at clinical stage FIGO IVB, exhibited severe chemotherapy-induced toxicity and postoperative complications, including chylous leakage. In contrast, the BRCA1/BRCA2 GDH patient is a 44-year-old female with high-grade serous ovarian cancer at clinical stage FIGO IIIC, tolerated chemotherapy well. Both patients experienced clinical benefit from Olaparib maintenance therapy. Genetic testing confirmed pathogenic variants in both cases, revealing distinct clinical trajectories influenced by different GDH profiles. Our findings suggest that different GDH combinations may influence chemotherapy tolerance and therapeutic effectiveness in OC. BRCA1/BRIP1 GDH patients may require personalized dose adjustments to mitigate toxicity and optimize efficacy. This study underscores the clinical significance of GDH heterogeneity and the importance of comprehensive genetic testing for guiding individualized treatment strategies. Future research should focus on expanding sample sizes and conducting in-depth functional analyses to further clarify the clinical implications of different GDH types, ultimately refining treatment approaches for GDH-associated OC. |
| format | Article |
| id | doaj-art-33e4605df22b4cb598f20398f18b097b |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-33e4605df22b4cb598f20398f18b097b2025-08-20T03:32:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.16143731614373Case Report: Clinical impact of BRCA1 and BRIP1 vs. BRCA1 and BRCA2 germline double heterozygosity in ovarian cancer: a comparative case studyLimei Zheng0Qianyuan Zhu1Qianyuan Zhu2Fenglan Zhang3Hao Qiu4Lan Qin5Jianhua Yang6Ming Qi7Ming Qi8Ming Qi9Ming Qi10Department of Obstetrics and Gynecology in Sir Run Shaw Hospital, School of Medicine, Zhejiang University, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, ChinaPolytechnic Institute of Zhejiang University, Hangzhou, Zhejiang, ChinaCenter for Clinical Genetics and Genomics, DIAN Diagnostics, Hangzhou, Zhejiang, ChinaCenter for Clinical Genetics and Genomics, DIAN Diagnostics, Hangzhou, Zhejiang, ChinaCenter for Clinical Genetics and Genomics, DIAN Diagnostics, Hangzhou, Zhejiang, ChinaCenter for Clinical Genetics and Genomics, DIAN Diagnostics, Hangzhou, Zhejiang, ChinaDepartment of Obstetrics and Gynecology in Sir Run Shaw Hospital, School of Medicine, Zhejiang University, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Department of Laboratory Medicine, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, ChinaDIAN Diagnostics, Hangzhou, Zhejiang, ChinaCenter for Precision Medicine, Zhejiang-California International NanoSystems Institute, Hangzhou, ChinaDepartment of Pathology and Laboratory of Medicine, University of Rochester Medical Centre, Rochester, NY, United StatesOvarian cancer (OC) is a highly heterogeneous malignancy influenced by germline genetic factors, with BRCA1/2 mutations being well-established risk factors. Germline double heterozygosity (GDH), particularly involving rare combinations, remains poorly understood. This study presents the first report of BRCA1/BRIP1 GDH in a case of Chinese OC patients and compares their clinical characteristics and treatment responses to a patient with BRCA1/BRCA2 GDH. The BRCA1/BRIP1 GDH patient is a 46-year-old female diagnosed with advanced ovarian adenocarcinoma at clinical stage FIGO IVB, exhibited severe chemotherapy-induced toxicity and postoperative complications, including chylous leakage. In contrast, the BRCA1/BRCA2 GDH patient is a 44-year-old female with high-grade serous ovarian cancer at clinical stage FIGO IIIC, tolerated chemotherapy well. Both patients experienced clinical benefit from Olaparib maintenance therapy. Genetic testing confirmed pathogenic variants in both cases, revealing distinct clinical trajectories influenced by different GDH profiles. Our findings suggest that different GDH combinations may influence chemotherapy tolerance and therapeutic effectiveness in OC. BRCA1/BRIP1 GDH patients may require personalized dose adjustments to mitigate toxicity and optimize efficacy. This study underscores the clinical significance of GDH heterogeneity and the importance of comprehensive genetic testing for guiding individualized treatment strategies. Future research should focus on expanding sample sizes and conducting in-depth functional analyses to further clarify the clinical implications of different GDH types, ultimately refining treatment approaches for GDH-associated OC.https://www.frontiersin.org/articles/10.3389/fonc.2025.1614373/fullBRCA1BRCA2BRIP1germline double heterozygosityovarian cancercase report |
| spellingShingle | Limei Zheng Qianyuan Zhu Qianyuan Zhu Fenglan Zhang Hao Qiu Lan Qin Jianhua Yang Ming Qi Ming Qi Ming Qi Ming Qi Case Report: Clinical impact of BRCA1 and BRIP1 vs. BRCA1 and BRCA2 germline double heterozygosity in ovarian cancer: a comparative case study Frontiers in Oncology BRCA1 BRCA2 BRIP1 germline double heterozygosity ovarian cancer case report |
| title | Case Report: Clinical impact of BRCA1 and BRIP1 vs. BRCA1 and BRCA2 germline double heterozygosity in ovarian cancer: a comparative case study |
| title_full | Case Report: Clinical impact of BRCA1 and BRIP1 vs. BRCA1 and BRCA2 germline double heterozygosity in ovarian cancer: a comparative case study |
| title_fullStr | Case Report: Clinical impact of BRCA1 and BRIP1 vs. BRCA1 and BRCA2 germline double heterozygosity in ovarian cancer: a comparative case study |
| title_full_unstemmed | Case Report: Clinical impact of BRCA1 and BRIP1 vs. BRCA1 and BRCA2 germline double heterozygosity in ovarian cancer: a comparative case study |
| title_short | Case Report: Clinical impact of BRCA1 and BRIP1 vs. BRCA1 and BRCA2 germline double heterozygosity in ovarian cancer: a comparative case study |
| title_sort | case report clinical impact of brca1 and brip1 vs brca1 and brca2 germline double heterozygosity in ovarian cancer a comparative case study |
| topic | BRCA1 BRCA2 BRIP1 germline double heterozygosity ovarian cancer case report |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1614373/full |
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