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. 2018 Aug 13;12(1):39.
doi: 10.1186/s40246-018-0171-5.

BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: comparison with breast cancer variants in a similar population

Florencia C Cardoso  1 , Susana Goncalves  2 , Pablo G Mele  3 , Natalia C Liria  1 , Leonardo Sganga  2 , Ignacio Diaz Perez  2 , Ernesto J Podesta  3 , Angela R Solano  4   5
Affiliations

BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: comparison with breast cancer variants in a similar population

Florencia C Cardoso et al. Hum Genomics. .

Abstract

Background: Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presence of a BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can further benefit from the detection of carriers in the family. Germline sequence and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial ovarian cancer (EOC) patients. The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with ovarian serous carcinoma, with a view to adequately selecting patients for prevention through family counseling and correlating this frequency with platinum sensitivity as a guidance to identify patients eligible for iPARP in our population.

Results: A total of 96 patients carried a pathogenic germline mutation, accounting for an overall 24.1% mutation incidence. Among mutation carriers, BRCA1 showed 62.5% incidence, BRCA2 rendered 36.5%, and one patient exhibited a mutation in both genes. Three pathogenic mutations were recurrent mutations detected five, three, and four times and represented 12.5% of the mutated samples. Worth highlighting, a 50% mutation incidence was detected when breast and ovarian cancer coexisted in the same patient. Novel mutations amounted to 9.4% of the total mutations, as compared to 4.7% in breast cancer. Forty out of 60 BRCA1 mutations were beyond the ovarian cancer cluster region (OCCR), in stark contrast with 22 out of 36 BRCA2 mutations being inside the OCCR. Taken together, germline BRCA1/2 mutations in EOC patients showed a distinct mutational spectrum compared to our previously published data on breast cancer patients.

Conclusions: In sum, our study provides novel data on ovarian BRCA1/2 mutation prevalence worldwide, enhances adequate patient selection for family counseling and prevention, and sheds light on the benefits of iPARP treatment.

Keywords: BRCA1/2 and ovarian cancer; Ovarian cancer; iPARP treatment.

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Conflict of interest statement

Routine procedure included signing a written informed consent to genetic testing (including anonymized disclosure of the data) from each patient, approved by the Ethics Committee from CEMIC and a Pretest Counseling for Susceptibility Testing (purpose of testing), as described in the American Society of Clinical Oncology Policy Statement Update.

SG is the medical director in AstraZeneca Argentina and Uruguay MC. LS is the diagnosis manager in AstraZeneca Argentina MC. IDP is the oncology medical manager in AstraZeneca Argentina and Uruguay MC. The other authors declare that they have no competing interest.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Schematic representation of the 96 BRCA1/2 pathogenic mutations detected in 398 patients with diagnosis of epithelial ovarian cancer
See this image and copyright information in PMC

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