Suppression of BRCA2 expression by siRNA or shRNA increased the sensitivity to 6-TG- and olaparib-induced apoptosis but did not affect cancer cell response to taxane.
Combined with our demonstration of BRCA2 expression in adult liver tissue, the evidence implies that inactivation of BRCA2 may play some role in development or progression of hepatocellular carcinoma and might predispose carriers of mutant alleles to liver malignancies.
Taken together, our data suggest disruption of BRCA1 and/or BRCA2 gene expression in certain epithelial cancer cell lines of the ovary, prostate, and breast.
Promoter regions of FANCA, BRCA1 and BRCA2 displayed recurrent alterations in the methylation levels in cancer samples as compared to buccal swabs controls.
Uncovering other genes that become mutated subsequent to BRCA1/BRCA2 inactivation during cancer development will be helpful for more effective treatments.
We report that BRCA2 downregulation sensitized multiple human tumor cell lines (but not non-cancer human kidney cells) to olaparib and, combined with olaparib, increased aneuploidy and chromosomal translocations in human tumor cells.
To understand this paradoxical condition of a tumour suppressor protein facilitating cancer cell survival, in the current study, we investigate the role of RAD52 overexpression in BRCA2 deficient cells.
BRCA2 inactivation by depletion or cancer-causing mutations instigates RNAPII accumulation and R-loop accrual at PPP sites in actively transcribed genes, accompanied by γH2AX formation marking DNA breakage, which is reduced by ERCC4 endonuclease depletion.
BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2.
Humans with inherited heterozygous BRCA2 mutations have an increased risk of developing cancer; however, what triggers carcinogenesis in these individuals is unclear.Tan et al. find that environmental and metabolic aldehydes pose a threat to these individuals by promoting degradation of wild-type BRCA2 protein, thereby predisposing them to genomic instability and perhaps to cancer.
Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers.
In addition, results from radiation-induced chromatid break assay performed on lymphocytes obtained from 9 BRCA heterozygotes (8 BRCA1, 1 BRCA2) were compared to results from a control group of 18 women with no cancer history.
Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer.
Genetic counseling (GC) and germline genetic testing (GT) for BRCA1 and BRCA2 are considered standard of care for patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC).
Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 or components of the Fanconi anemia (FA) complex incite genomic instability and predispose to malignancy.
However, the acquired resistance to PARP inhibitors has created a need for new chemotherapeutic strategies to target <i>BRCA2.</i> The present systematic review collects and analyses the role of <i>BRCA2</i> alterations to be used in early diagnosis of an inherited syndrome associated with familiar cancer and as a prognostic and predictive biomarker for the management of pancreatic cancer patients.
Data from the IMPACT study ( ClinicalTrials.gov NCT00261456) that the cancer detection rate is substantially elevated in BRCA1 and BRCA2 carriers at prostate specific antigen greater than 3 ng/ml has helped establish the importance of close prostate specific antigen screening in these men.
Disruption of these BRCA2 interactions by cancer-associated mutations results in increased cytokinetic defects but has no effect on BRCA2-dependent homologous recombination repair of DNA damage.
Although BRCA1 and BRCA2 have some shared functions in cancer predisposition and therapy response, there are also key differences indicating divergent roles for each protein.
The fact that neither Rb1 nor BRCA2 appears to be inactivated in the majority of head-and-neck cancers suggests that novel tumor-suppressor genes are involved.
A flurry of articles on the structure of different domains of BRCA1 and BRCA2 have not only shed light on the biology of these proteins but have also raised hopes that these data could eventually be used to infer cancer association for a large number of inherited missense mutations whose effect on protein function is unclear.