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Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients

SIMPLE SUMMARY: The availability of multiple gene panel testing allows us to identify germline pathogenic variants of validated cancer genes. We evaluated the prevalence and clinical/prognostic impact of deleterious germline mutations in OC patients. Germline panel testing should be performed for al...

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Autores principales: Imterat, Majdi, Harter, Philipp, Rhiem, Kerstin, Heitz, Florian, Schneider, Stephanie, Concin, Nicole, Moubarak, Malak, Welz, Julia, Vrentas, Vasileios, Traut, Alexander, Hahnen, Eric, Schmutzler, Rita, du Bois, Andreas, Ataseven, Beyhan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177155/
https://www.ncbi.nlm.nih.gov/pubmed/37174000
http://dx.doi.org/10.3390/cancers15092534
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author Imterat, Majdi
Harter, Philipp
Rhiem, Kerstin
Heitz, Florian
Schneider, Stephanie
Concin, Nicole
Moubarak, Malak
Welz, Julia
Vrentas, Vasileios
Traut, Alexander
Hahnen, Eric
Schmutzler, Rita
du Bois, Andreas
Ataseven, Beyhan
author_facet Imterat, Majdi
Harter, Philipp
Rhiem, Kerstin
Heitz, Florian
Schneider, Stephanie
Concin, Nicole
Moubarak, Malak
Welz, Julia
Vrentas, Vasileios
Traut, Alexander
Hahnen, Eric
Schmutzler, Rita
du Bois, Andreas
Ataseven, Beyhan
author_sort Imterat, Majdi
collection PubMed
description SIMPLE SUMMARY: The availability of multiple gene panel testing allows us to identify germline pathogenic variants of validated cancer genes. We evaluated the prevalence and clinical/prognostic impact of deleterious germline mutations in OC patients. Germline panel testing should be performed for all patients with ovarian cancer. Better prognosis was found for germline mutated ovarian cancer patients. Endometrioid and clear cell histology subtypes show more deleterious mutations in other genes. ABSTRACT: Data on deleterious variants in genes other than BRCA1/2 remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk(®) 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 BRCA1/2 mutations, and (C) deleterious mutations in other genes. A total of 702 patients met the inclusion criteria. Of these 17.4% (n = 122) showed BRCA1/2 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, p < 0.001) and 3-year progression-free survival (PFS) only for cohort B (58.1% vs. 36.9%/41.6% in cohort A/C, p = 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 BRCA1/2. Germline mutations demonstrate in our cohort a prognostic factor and predict better prognosis for OC patients.
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spelling pubmed-101771552023-05-13 Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients Imterat, Majdi Harter, Philipp Rhiem, Kerstin Heitz, Florian Schneider, Stephanie Concin, Nicole Moubarak, Malak Welz, Julia Vrentas, Vasileios Traut, Alexander Hahnen, Eric Schmutzler, Rita du Bois, Andreas Ataseven, Beyhan Cancers (Basel) Article SIMPLE SUMMARY: The availability of multiple gene panel testing allows us to identify germline pathogenic variants of validated cancer genes. We evaluated the prevalence and clinical/prognostic impact of deleterious germline mutations in OC patients. Germline panel testing should be performed for all patients with ovarian cancer. Better prognosis was found for germline mutated ovarian cancer patients. Endometrioid and clear cell histology subtypes show more deleterious mutations in other genes. ABSTRACT: Data on deleterious variants in genes other than BRCA1/2 remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk(®) 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 BRCA1/2 mutations, and (C) deleterious mutations in other genes. A total of 702 patients met the inclusion criteria. Of these 17.4% (n = 122) showed BRCA1/2 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, p < 0.001) and 3-year progression-free survival (PFS) only for cohort B (58.1% vs. 36.9%/41.6% in cohort A/C, p = 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 BRCA1/2. Germline mutations demonstrate in our cohort a prognostic factor and predict better prognosis for OC patients. MDPI 2023-04-28 /pmc/articles/PMC10177155/ /pubmed/37174000 http://dx.doi.org/10.3390/cancers15092534 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Imterat, Majdi
Harter, Philipp
Rhiem, Kerstin
Heitz, Florian
Schneider, Stephanie
Concin, Nicole
Moubarak, Malak
Welz, Julia
Vrentas, Vasileios
Traut, Alexander
Hahnen, Eric
Schmutzler, Rita
du Bois, Andreas
Ataseven, Beyhan
Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177155/
https://www.ncbi.nlm.nih.gov/pubmed/37174000
http://dx.doi.org/10.3390/cancers15092534
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