In summary, this study shows that low BRCA1 and ERCC1 expression correlate with improved survival in advanced OC and HDAC inhibition induces synergistic cytotoxicity with platinum in vitro.
BRCA1 mutations are rare in sporadic cancers, but loss of BRCA1 resulting from reduced expression or incorrect subcellular localization is postulated to be important in non-familial breast and ovarian cancers.
We hypothesized that changes in gene expression profiles within the histologically normal fallopian tube epithelium of BRCA1 mutation carriers would overlap with the expression profiles in BRCA1-mutated ovarian carcinomas and represent a BRCA1 preneoplastic signature.
Our findings indicate how BRCA1-IRIS overexpression prevents chemotherapy-induced cell death by upregulating expression of survivin, and they highlight this regulatory cascade as a candidate focus to improve treatment of advanced drug-resistant ovarian cancers.
The use of maintenance olaparib in women with high-grade serous ovarian cancer is not cost-effective regardless of whether BRCA1/2 testing is used to direct treatment.
Finally, concomitant increased mutant BRCA1 and decreased 53BP1 protein expression occur in clinical samples of BRCA1-mutated recurrent ovarian carcinomas that have developed resistance to platinum.
Thus, since a wide variety of human malignancies like breast and ovarian cancers have a decreased ability to undergo apoptosis, this could be due to lack/decreased levels of functional BRCA1 proteins.
Low or no expression of BRCA1 in breast and ovarian cancers is associated with a good clinical response to treatment with platinum therapies and PARP1 inhibitors.
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.
EMSY is located within an amplicon in sporadic breast and ovarian cancers, suggesting that its overexpression may mimic the effects of BRCA2 inactivation.
BRCA1 expression is decreased or absent in a significant proportion of sporadic breast and ovarian cancers, suggesting a wider role in these tumor types.