A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their Outcomes
DNA damage response (DDR) is important for maintaining genomic integrity of the cell. Aberrant DDR pathways lead to accumulation of DNA damage, genomic instability and malignant transformations. Gene mutations have been proven to be associated with epithelial ovarian cancer, and the majority of the...
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/2227-9059/9/10/1384 |
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| author | Ying-Cheng Chiang Po-Han Lin Tzu-Pin Lu Kuan-Ting Kuo Yi-Jou Tai Heng-Cheng Hsu Chia-Ying Wu Chia-Yi Lee Hung Shen Chi-An Chen Wen-Fang Cheng |
| author_facet | Ying-Cheng Chiang Po-Han Lin Tzu-Pin Lu Kuan-Ting Kuo Yi-Jou Tai Heng-Cheng Hsu Chia-Ying Wu Chia-Yi Lee Hung Shen Chi-An Chen Wen-Fang Cheng |
| author_sort | Ying-Cheng Chiang |
| collection | DOAJ |
| description | DNA damage response (DDR) is important for maintaining genomic integrity of the cell. Aberrant DDR pathways lead to accumulation of DNA damage, genomic instability and malignant transformations. Gene mutations have been proven to be associated with epithelial ovarian cancer, and the majority of the literature has focused on <i>BRCA</i>. In this study, we investigated the somatic mutation of DNA damage response genes in epithelial ovarian cancer patients using a multiple-gene panel with next-generation sequencing. In all, 69 serous, 39 endometrioid and 64 clear cell carcinoma patients were enrolled. Serous carcinoma patients (69.6%) had higher percentages of DDR gene mutations compared with patients with endometrioid (33.3%) and clear cell carcinoma (26.6%) (<i>p</i> < 0.001, chi-squared test). The percentages of DDR gene mutations in patients with recurrence (53.9 vs. 32.9% <i>p</i> = 0.006, chi-squared test) or cancer-related death (59.2 vs. 34.4% <i>p</i> = 0.001, chi-squared test) were higher than those without recurrence or living patients. In endometrioid carcinoma, patients with ≥2 DDR gene mutations had shorter PFS (<i>p</i> = 0.0035, log-rank test) and OS (<i>p</i> = 0.015, log-rank test) than those with one mutation or none. In clear cell carcinoma, patients with ≥2 DDR gene mutations had significantly shorter PFS (<i>p</i> = 0.0056, log-rank test) and OS (<i>p</i> = 0.0046, log-rank test) than those with 1 DDR mutation or none. In the EOC patients, somatic DDR gene mutations were associated with advanced-stage tumor recurrence and tumor-related death. Type I EOC patients with DDR mutations had an unfavorable prognosis, especially for clear cell carcinoma. |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T06:42:38Z |
| publishDate | 2021-10-01 |
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| spelling | doaj.art-a2868da519934160a5a939b712793c692023-11-22T17:31:04ZengMDPI AGBiomedicines2227-90592021-10-01910138410.3390/biomedicines9101384A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their OutcomesYing-Cheng Chiang0Po-Han Lin1Tzu-Pin Lu2Kuan-Ting Kuo3Yi-Jou Tai4Heng-Cheng Hsu5Chia-Ying Wu6Chia-Yi Lee7Hung Shen8Chi-An Chen9Wen-Fang Cheng10Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100226, TaiwanDepartment of Medical Genetics, National Taiwan University Hospital, Taipei 100226, TaiwanInstitute of Epidemiology and Preventive Medicine, Department of Public Health, National Taiwan University, Taipei 100025, TaiwanDepartment of Pathology, College of Medicine, National Taiwan University, Taipei 100225, TaiwanDepartment of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei 100226, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100225, TaiwanDepartment of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei 100226, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100225, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100225, TaiwanDepartment of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100226, TaiwanDepartment of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100226, TaiwanDNA damage response (DDR) is important for maintaining genomic integrity of the cell. Aberrant DDR pathways lead to accumulation of DNA damage, genomic instability and malignant transformations. Gene mutations have been proven to be associated with epithelial ovarian cancer, and the majority of the literature has focused on <i>BRCA</i>. In this study, we investigated the somatic mutation of DNA damage response genes in epithelial ovarian cancer patients using a multiple-gene panel with next-generation sequencing. In all, 69 serous, 39 endometrioid and 64 clear cell carcinoma patients were enrolled. Serous carcinoma patients (69.6%) had higher percentages of DDR gene mutations compared with patients with endometrioid (33.3%) and clear cell carcinoma (26.6%) (<i>p</i> < 0.001, chi-squared test). The percentages of DDR gene mutations in patients with recurrence (53.9 vs. 32.9% <i>p</i> = 0.006, chi-squared test) or cancer-related death (59.2 vs. 34.4% <i>p</i> = 0.001, chi-squared test) were higher than those without recurrence or living patients. In endometrioid carcinoma, patients with ≥2 DDR gene mutations had shorter PFS (<i>p</i> = 0.0035, log-rank test) and OS (<i>p</i> = 0.015, log-rank test) than those with one mutation or none. In clear cell carcinoma, patients with ≥2 DDR gene mutations had significantly shorter PFS (<i>p</i> = 0.0056, log-rank test) and OS (<i>p</i> = 0.0046, log-rank test) than those with 1 DDR mutation or none. In the EOC patients, somatic DDR gene mutations were associated with advanced-stage tumor recurrence and tumor-related death. Type I EOC patients with DDR mutations had an unfavorable prognosis, especially for clear cell carcinoma.https://www.mdpi.com/2227-9059/9/10/1384epithelial ovarian cancerDNA damage responsesomatic mutationclear cell carcinoma |
| spellingShingle | Ying-Cheng Chiang Po-Han Lin Tzu-Pin Lu Kuan-Ting Kuo Yi-Jou Tai Heng-Cheng Hsu Chia-Ying Wu Chia-Yi Lee Hung Shen Chi-An Chen Wen-Fang Cheng A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their Outcomes Biomedicines epithelial ovarian cancer DNA damage response somatic mutation clear cell carcinoma |
| title | A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their Outcomes |
| title_full | A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their Outcomes |
| title_fullStr | A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their Outcomes |
| title_full_unstemmed | A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their Outcomes |
| title_short | A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their Outcomes |
| title_sort | dna damage response gene panel for different histologic types of epithelial ovarian carcinomas and their outcomes |
| topic | epithelial ovarian cancer DNA damage response somatic mutation clear cell carcinoma |
| url | https://www.mdpi.com/2227-9059/9/10/1384 |
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