1. Reclassification of BRCA1 and BRCA2 variants of uncertain significance in patients with epithelial ovarian cancer.
- Author
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Dae Hoon Jeong, Jung Mi Byun, Eun Kyoung You, Joo Ran Kim, Ha Young Park, Kyung Bog Lee, and Eunhye Cho
- Subjects
OVARIAN epithelial cancer ,BRCA genes ,MOLECULAR pathology ,MEDICAL genomics ,MEDICAL genetics - Abstract
Objective: Reclassification of variants of uncertain significance (VUS) may allow for improved cancer prevention, screening, targeted therapy, as well as surgical and reproductive decisionmaking. We reinterpreted BRCA1/2 VUS results in patients with epithelial ovarian cancer and assessed whether the clinical significance of VUS was changed. Methods: We retrospectively reviewed the medical records of 253 epithelial ovarian cancer patients who underwent BRCA1/2 genetic testing from 2010 to 2020. The VUSs in BRCA1/2 were reanalyzed using the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines (ACMG/AMP 2015 guidelines) and the VUS were reclassified into 5 categories: "pathogenic," "likely pathogenic," "VUS," "likely benign," and "benign." Results: Forty-nine patients were identified as carrying either one or more VUS in BRCA1/2. Among the 49 patients, 44 patients (89.9%) were reclassified as benign (including likely benign) or pathogenic (including likely pathogenic) variants. Four patients (8.2%) were reclassified as "pathogenic or likely pathogenic," 40 patients (81.6%) were reclassified as either "benign" or "likely benign," and the remaining 5 patients (10.2%) were still classified as VUS category. There was a family history of ovarian cancer or breast cancer in the group of patients reclassified as a pathogenic variant (p=0.053). Although there was no statistically significant difference in survival, the survival rate of patients classified as pathogenic was higher. Conclusion: Reclassification of VUS should be done periodically, which is crucial to improve clinical decision-making. In particular, reclassification is necessary for VUS patients with a family history of ovarian cancer or breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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