학술논문
Beyond BRCA1/2: Homologous Recombination Repair Genetic Profile in a Large Cohort of Apulian Ovarian Cancers.
Document Type
Article
Author
Turchiano, Antonella; Loconte, Daria Carmela; De Nola, Rosalba; Arezzo, Francesca; Chiarello, Giulia; Pantaleo, Antonino; Iacoviello, Matteo; Bagnulo, Rosanna; De Luisi, Annunziata; Perrelli, Sonia; Martino, Stefania; Ranieri, Carlotta; Garganese, Antonella; Stella, Alessandro; Forleo, Cinzia; Loizzi, Vera; Marinaccio, Marco; Cicinelli, Ettore; Cormio, Gennaro; Resta, Nicoletta
Source
Subject
*OVARIAN tumors
*GENETIC mutation
*
Language
ISSN
2072-6694
Abstract
Simple Summary: Ovarian cancer (OC) is the second most common gynecologic malignancy and the most common cause of death among women with gynecologic cancer. Despite significant improvements having been made over the past decades, OC remains one of the most challenging malignancies to treat. Targeted therapies, such as PARPi, have emerged as one of the most interesting treatments for OC, particularly in women with BRCA1 or BRCA2 mutations. or those with a dysfunctional homologous recombination repair pathway. The purpose of our study is to address the role of NGS-targeted resequencing in the clinical routine of OC, focusing not only on BRCA1/2 but also on the homologous recombination repair genetic profile. Background: Pathogenic variants in homologous recombination repair (HRR) genes other than BRCA1/2 have been associated with a high risk of ovarian cancer (OC). In current clinical practice, genetic testing is generally limited to BRCA1/2. Herein, we investigated the mutational status of both BRCA1/2 and 5 HRR genes in 69 unselected OC, evaluating the advantage of multigene panel testing in everyday clinical practice. Methods: We analyzed 69 epithelial OC samples using an NGS custom multigene panel of the 5 HRR pathways genes, beyond the genetic screening routine of BRCA1/2 testing. Results: Overall, 19 pathogenic variants (27.5%) were detected. The majority (21.7%) of patients displayed a deleterious mutation in BRCA1/2, whereas 5.8% harbored a pathogenic variant in one of the HRR genes. Additionally, there were 14 (20.3%) uncertain significant variants (VUS). The assessment of germline mutational status showed that a small number of variants (five) were not detected in the corresponding blood sample. Notably, we detected one BRIP1 and four BRCA1/2 deleterious variants in the low-grade serous and endometrioid histology OC, respectively. Conclusion: We demonstrate that using a multigene panel beyond BRCA1/2 improves the diagnostic yield in OC testing, and it could produce clinically relevant results. [ABSTRACT FROM AUTHOR]