Retrospective analysis of 77 patients with ovarian cancer undergoing genetic testing for BRCA1 and BRCA2 mutations

Background: Ovarian cancer (OC) is still a big killer in the field of female neoplastic disease, placing itself fifth as cause of death. In recent years, some genetic mutations have been analyzed within high grade serum OC. BRCA1-BRCA2 genes mutation is the most commonly observed in a proportion of patients with ovarian cancer not necessarily belonging to families expressing such alterations. Material (patients) and methods: A retrospective cohort of 77 OC patients were selected between 2014-2017. All patients samples were collected with appropriate consents and tested for germline BRCA1 and BRCA2 mutations after genetic counselling at the Department of Medical Genetics unit of University Hospital of Careggi in Florence. Genomic DNA was isolated from blood using FlexiGene DNA Kit.Targeted library preparation of BRCA1 and BRCA2 was performed using hybridization capture probes or multiplex PCR strategies and Illumina sequencing was carried out on the Illumina MiSeq following the manufacturer’s instructions. Data analysis, including alignment to the hg19 human reference genome and variant calling was done using GATK or SeqNext software package. All pathogenic germline variants were validated by Sanger sequencing. Results: Pathogenic mutations in BRCA genes were found in 23 out of 77 (29.9%) high grade malignant epithelial OC: 20 of them were in BRCA1 while 3 in BRCA2. The remaining 54 patients were wild type. Patients, after cytoreductive surgery, had chemotherapy of line I according to the carboplatin-paclitaxel scheme for 6 cycles. All 23 mutated patients, except for a platinum-resistant case (4-month progression time), had platinum sensitivity over 6 months. 16 patients over 20 with BRCA1 and BRCA2 mutations, received a chemotherapy II of line. Of these patients, 13 had a PFS greater than 6 months and 3 patients were resistant platinum. Ca 125 basal marker was positive (range of normality between 0-35) in more than 78.2% of cases, while Ca 125 on relapse was positive in 95.7% of cases. Conclusions: The differentiation of patients in subgroups related to the presence or absence of BRCA1 and BRCA2 genes and their variants, has allowed to identify in the mutated population a higher platinum sensitivity, also in subsequent lines of therapy and to undertake treatments with innovative molecules for OC such as PARP14-16 inhibitors, that partially modified the prognosis of this neoplasia by increasing the disease-free interval.