BRCA-Associated Ovarian Cancer: From Molecular Genetics to Risk Management

Abstract

Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposition, on pathology and clinical behavior of OC occurring in BRCA mutation carriers, and on the available options for managing asymptomatic carriers.

Prognostic significance ofBRCAmutations in ovarian cancer: an updated systematic review with meta-analysis

“…BRCA1/2 tumor suppressor genes are reported to be involved in DNA repair through homologous recombination, through which pathway genes are unable to repair DNA double-strand, resulting in genomic instability and having a tendency to malignant transformation [3]. On the other hand, the impairment of this pathway can also influence DNA cross-links by tumor cells, which can be induced by cisplatin, a chemotherapy agent for ovarian cancer.…”

Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology

“…Pathogenic mutations of this type are traditionally determined by Sanger sequencing. As well as the above-mentioned genetic alterations, large rearrangements should be identified by MLPA (Multiplex Ligation Probe Assay) or massive sequencing techniques (NGS, Next-Generation Sequencing), because the Sanger method cannot detect large rearrangements [43]. Given the crucial nature of the result, it is important for BRCA mutation tests to be done in accredited laboratories, with internal and external qualitycontrol systems [44].…”

Is Ovarian Cancer Prevention Currently Still a recommendation of Our Grandparents?

“…In addition, a more favorable prognosis has been reported for patients carrying BRCA2 mutations compared with patients with sporadic ovarian cancer, and this cancer does not occur in women with BRCA1mutations. 39 When the epithelium at the surface of an ovary is disrupted during ovulation, tubal epithelial cells of the fimbriae of the fallopian tube can move and implant in the ovary, thereby forming an inclusion cyst. It is possible that a serous carcinoma can subsequently develop.…”