Low BRCA1 expression correlates with increased chromosomal aberrations in primary ovarian carcinomas, and the junction sequences of somatic structural variants indicate diminished homologous recombination.
This study was designed to determine the frequency of three single nucleotide polymorphisms (SNPs) variants in BRCA1 gene and BRCA1 expression in Saudi females with ovarian cancer.
Our findings imply that genetic (e.g., BRCA1 inactivation) and NAD-dependent metabolic pathways are jointly involved in the malignant progression of ovarian cancer.
Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers.
Additionally, EGFR expression was higher in normal tissues of BRCA1-mutated patients, and was further increased in cancer tissues; EGFR levels were also significantly elevated in ovarian cancer with promoter hypermethylation-mediated inactivation of BRCA1.
Our study suggests that in OC <i>PD-1</i>/<i>PD-L1</i> mRNA-expression is controlled by <i>IFNγ</i> and affected by <i>TP53</i> and <i>BRCA1/2</i> mutations.
BRCA1 expression is decreased or absent in a significant proportion of sporadic breast and ovarian cancers, suggesting a wider role in these tumor types.
Our data support a tumour suppressor mechanism for BRCA1; somatic mutations and LOH may result in inactivation of BRCA1 in at least a small number of ovarian cancers.
Down-regulation of BRCA1 expression by hypermethylation of its promoter may account for some cases of ovarian cancer but this does not explain the cause of the majority of the disease.
Most importantly, BRCA1 hypermethylation proves to be a predictor of longer time to relapse and improved overall survival in ovarian cancer patients undergoing chemotherapy with cisplatin.
Aim of this study was to analyse the clinical impact of BRCA1 promoter gene methylation status in a homogenous cohort of high-grade serous ovarian cancer (HGSOC) patients.
BRCA1 promoter hypermethylation was identified in 2 of 49 families in which multiple women are affected by grade 3 breast cancer or high-grade serous ovarian cancer.