Dataset Information

BRCA1/2 Mutation Types Do Not Affect Prognosis in Ovarian Cancer Patients.

ABSTRACT:

Background

High grade serous ovarian carcinoma (HGSOC) is the most lethal type of epithelial ovarian cancer, with a prevalence of germline BRCA1/2 mutations as high as 20%. Our objective is to determine whether the location of mutations in the different domains of the BRCA1/2 genes affects the clinical outcome of HGSOC patients.

Methods

A total of 51 women with BRCA1 or BRCA2 mutated ovarian cancer were identified. Progression-free survival (PFS) and overall survival (OS) were analyzed.

Results

In our study cohort, 35 patients were carriers of germline mutations in BRCA1 and 16 in BRCA2. The median PFS time following completion of the primary therapy was 23.8 months (95% CI 20.1-27.5) and the median OS was 92.9 months (95% CI 69.8-116.1) in all BRCA carriers. After multivariate analysis, no significant association among the location or type of BRCA1/2 mutation with PFS or OS was identified. Notably, significant differences in PFS between carriers of identical mutations in the same BRCA gene were detected.

Conclusions

Among HGSOC patients, BRCA1/2 carriers with mutations in different locations of the genes show no significant difference in survival outcomes, in terms of PFS and OS, suggesting the potential effect of other genetic abnormalities and co-contributing risk factors.

SUBMITTER: Liontos M

PROVIDER: S-EPMC8628789 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

<i>BRCA1/2</i> Mutation Types Do Not Affect Prognosis in Ovarian Cancer Patients.

Liontos Michalis M Zografos Eleni E Zoumpourlis Panagiotis P Andrikopoulou Angeliki A Svarna Anna A Fiste Oraianthi O Kunadis Elena E Papatheodoridi Alkistis Maria AM Kaparelou Maria M Koutsoukos Konstantinos K Thomakos Nikoloas N Haidopoulos Dimitrios D Rodolakis Alexandros A Dimopoulos Meletios-Athanasios MA Zagouri Flora F

Current oncology (Toronto, Ont.) 20211103 6

<h4>Background</h4>High grade serous ovarian carcinoma (HGSOC) is the most lethal type of epithelial ovarian cancer, with a prevalence of germline <i>BRCA1/2</i> mutations as high as 20%. Our objective is to determine whether the location of mutations in the different domains of the <i>BRCA1/2</i> genes affects the clinical outcome of HGSOC patients.<h4>Methods</h4>A total of 51 women with <i>BRCA1</i> or <i>BRCA2</i> mutated ovarian cancer were identified. Progression-free survival (PFS) and ov ...[more]

PMID: 34898566

Similar Datasets

Project description:BACKGROUND:Poly (ADP-ribose) polymerase inhibitors targeting BRCA1/2 mutations are available for treating patients with high-grade serous ovarian cancer. These treatments may be more appropriately directed to patients who might respond if the tumor tissue is additionally tested by next-generation sequencing with a multi-gene panel and Sanger sequencing of a blood sample. In this study, we compared the results obtained using the next-generation sequencing multi-gene panel to a known germline BRCA1/2 mutational state determined by conventional Sanger sequencing to evaluate the landscape of somatic mutations in high-grade serous ovarian cancer tumors. METHODS:Cancer tissue from 98 patients with high-grade serous ovarian cancer who underwent Sanger sequencing for germline BRCA1/2 analysis were consecutively analyzed for somatic mutations using a next-generation sequencing 170-gene panel. RESULTS:Twenty-four patients (24.5%) showed overall BRCA1/2 mutations. Seven patients (7.1%) contained only somatic BRCA1/2 mutations with wild-type germline BRCA1/2, indicating acquired mutation of BRCA1/2. Three patients (3.1%) showed reversion of germline BRCA1 mutations. Among the 14 patients (14.3%) with both germline and somatic mutations in BRCA1/2, two patients showed different variations of BRCA1/2 mutations. The next-generation sequencing panel test for somatic mutation detected other pathogenic variations including RAD51D and ARID1A, which are possible targets of poly (ADP-ribose) polymerase inhibitors. Compared to conventional Sanger sequencing alone, next-generation sequencing-based tissue analysis increased the number of candidates for poly (ADP-ribose) polymerase inhibitor treatment from 17.3% (17/98) to 26.5% (26/98). CONCLUSIONS:Somatic mutation analysis by next-generation sequencing, in addition to germline BRCA1/2 mutation analysis, should become the standard of care for managing women with high-grade serous ovarian cancer to widen the indication of poly (ADP-ribose) polymerase inhibitors.