Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients
Data on deleterious variants in genes other than <i>BRCA1/2</i> remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk<sup>®</sup> germline gene panel testing between 2011 and 2020. Patients with testing after relapse were excluded...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/9/2534 |
| _version_ | 1797602889011560448 |
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| author | Majdi Imterat Philipp Harter Kerstin Rhiem Florian Heitz Stephanie Schneider Nicole Concin Malak Moubarak Julia Welz Vasileios Vrentas Alexander Traut Eric Hahnen Rita Schmutzler Andreas du Bois Beyhan Ataseven |
| author_facet | Majdi Imterat Philipp Harter Kerstin Rhiem Florian Heitz Stephanie Schneider Nicole Concin Malak Moubarak Julia Welz Vasileios Vrentas Alexander Traut Eric Hahnen Rita Schmutzler Andreas du Bois Beyhan Ataseven |
| author_sort | Majdi Imterat |
| collection | DOAJ |
| description | Data on deleterious variants in genes other than <i>BRCA1/2</i> remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk<sup>®</sup> germline gene panel testing between 2011 and 2020. Patients with testing after relapse were excluded. The cohort was divided into three groups: (A) no mutations, (B) deleterious <i>BRCA1/2</i> mutations, and (C) deleterious mutations in other genes. A total of 702 patients met the inclusion criteria. Of these 17.4% (n = 122) showed <i>BRCA1/2</i> mutations and a further 6.0% (n = 42) in other genes. Three-year overall survival (OS) of the entire cohort was significantly longer in patients with germline mutations (85%/82.8% for cohort B/C vs. 70.2% for cohort A, <i>p</i> < 0.001) and 3-year progression-free survival (PFS) only for cohort B (58.1% vs. 36.9%/41.6% in cohort A/C, <i>p</i> = 0.002). In multivariate analysis for the subgroup of advanced-stages of high-grade serous OC, both cohorts B/C were found to be independent factors for significantly better outcome, cohort C for OS (HR 0.46; 95% CI 0.25–0.84), and cohort B for both OS and PFS (HR 0.40; 95% CI 0.27–0.61 and HR 0.49; 95% CI 0.37–0.66, respectively). Germline mutations were detected in a quarter of OC patients, and a quarter of those in genes other than <i>BRCA1/2</i>. Germline mutations demonstrate in our cohort a prognostic factor and predict better prognosis for OC patients. |
| first_indexed | 2024-03-11T04:21:48Z |
| format | Article |
| id | doaj.art-11afbed8b3314547895462535c50c15c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T04:21:48Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-11afbed8b3314547895462535c50c15c2023-11-17T22:41:04ZengMDPI AGCancers2072-66942023-04-01159253410.3390/cancers15092534Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma PatientsMajdi Imterat0Philipp Harter1Kerstin Rhiem2Florian Heitz3Stephanie Schneider4Nicole Concin5Malak Moubarak6Julia Welz7Vasileios Vrentas8Alexander Traut9Eric Hahnen10Rita Schmutzler11Andreas du Bois12Beyhan Ataseven13Department of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyDepartment of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, 50931 Cologne, GermanyDepartment of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyDepartment of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyDepartment of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyDepartment of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyDepartment of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyDepartment of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyDepartment of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, 50931 Cologne, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, 50931 Cologne, GermanyDepartment of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyDepartment of Gynaecology and Gynaecologic Oncology, Kliniken Essen Mitte (KEM), 45136 Essen, GermanyData on deleterious variants in genes other than <i>BRCA1/2</i> remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk<sup>®</sup> germline gene panel testing between 2011 and 2020. Patients with testing after relapse were excluded. The cohort was divided into three groups: (A) no mutations, (B) deleterious <i>BRCA1/2</i> mutations, and (C) deleterious mutations in other genes. A total of 702 patients met the inclusion criteria. Of these 17.4% (n = 122) showed <i>BRCA1/2</i> mutations and a further 6.0% (n = 42) in other genes. Three-year overall survival (OS) of the entire cohort was significantly longer in patients with germline mutations (85%/82.8% for cohort B/C vs. 70.2% for cohort A, <i>p</i> < 0.001) and 3-year progression-free survival (PFS) only for cohort B (58.1% vs. 36.9%/41.6% in cohort A/C, <i>p</i> = 0.002). In multivariate analysis for the subgroup of advanced-stages of high-grade serous OC, both cohorts B/C were found to be independent factors for significantly better outcome, cohort C for OS (HR 0.46; 95% CI 0.25–0.84), and cohort B for both OS and PFS (HR 0.40; 95% CI 0.27–0.61 and HR 0.49; 95% CI 0.37–0.66, respectively). Germline mutations were detected in a quarter of OC patients, and a quarter of those in genes other than <i>BRCA1/2</i>. Germline mutations demonstrate in our cohort a prognostic factor and predict better prognosis for OC patients.https://www.mdpi.com/2072-6694/15/9/2534<i>BRCA1/2</i><i>RAD51C/D</i><i>BRIP1</i><i>PALB2</i>ovarian cancersurvival |
| spellingShingle | Majdi Imterat Philipp Harter Kerstin Rhiem Florian Heitz Stephanie Schneider Nicole Concin Malak Moubarak Julia Welz Vasileios Vrentas Alexander Traut Eric Hahnen Rita Schmutzler Andreas du Bois Beyhan Ataseven Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients Cancers <i>BRCA1/2</i> <i>RAD51C/D</i> <i>BRIP1</i> <i>PALB2</i> ovarian cancer survival |
| title | Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients |
| title_full | Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients |
| title_fullStr | Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients |
| title_full_unstemmed | Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients |
| title_short | Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients |
| title_sort | incidence and prognostic impact of deleterious germline mutations in primary advanced ovarian carcinoma patients |
| topic | <i>BRCA1/2</i> <i>RAD51C/D</i> <i>BRIP1</i> <i>PALB2</i> ovarian cancer survival |
| url | https://www.mdpi.com/2072-6694/15/9/2534 |
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