It is thought that over forty percent of an individual's risk of developing prostate cancer (PCa) is related to familial and genetic factors. Although multiple genes have been implicated in the development of PCa, few confer as high a risk as mutations in the genes associated with early-onset breast cancer (BRCA1 and BRCA2). Not only do mutations in BRCA genes increase the risk of PCa, but they...

BACKGROUND Germline pathogenic mutations in cancer susceptibility genes result in inherited cancer syndromes. In the Afrikaner population of South Africa (SA), three founder mutations in the BRCA genes that lead to hereditary breast and ovarian cancer syndrome (HBOCS) have been identified. OBJECTIVES To investigate the uptake and type of molecular testing performed on patients for HBOCS, to d...

BACKGROUND Deleterious mutations in the BRCA genes are responsible for a small, but significant, proportion of breast and ovarian cancers (5 - 10 %). Proof of de novo mutations in hereditary breast/ovarian cancer (HBOC) families is rare, in contrast to founder mutations, thousands of years old, that may be carried by as much as 1 % of a population. Thus, if mutations favoring cancer survive sel...

Homologous recombination (HR) and base excision repair (BER) are two of the major DNA-repair pathways. The proteins encoded by breast-related cancer antigen (BRCA) and poly(adenosine diphosphate-ribose) polymerases (PARP) are involved in HR and BER, respectively. Tumors with HR deficiency, including those in BRCA mutation carriers, are sensitive to BER blockade via PARP inhibitors. These repres...

BACKGROUND High-grade serous ovarian cancers are a distinct histological subtype of ovarian cancer often characterised by a dysfunctional BRCA/Fanconi anaemia (BRCA/FA) pathway, which is critical to the homologous recombination DNA repair machinery. An impaired BRCA/FA pathway sensitises tumours to the treatment with DNA cross-linking agents and to PARP inhibitors. The vast majority of inactiva...

We previously reported that BRCA1/2-mutated fallopian tube epithelium (FTE) collected during the luteal phase exhibits gene expression profiles more closely resembling that of high-grade serous carcinoma (HGSC) specimens than FTE collected during the follicular phase or from control patients. Since the luteal phase is characterised by high levels of progesterone, we determined whether the expre...

Abstract BACKGROUND Despite progress in the treatment of brain metastasis (BrM) for HER2+ breast cancer (BC), outcomes patients with HER2-negative BC BrM remain poor. Current standard care consists local therapies, including surgery and radiotherapy, followed by systemic therapy. Preclinical studies show inhibitors poly(ADP-ribose) polymerase (PARP) are effective radiation therapy as a DNA dama...

Treatment with PARP inhibitors in the maintenance of ovarian cancer has been a revolution natural history disease, especially those cases carrying BRCA mutations. Within this population, it described that alterations RING region BRCA-1 confer resistance to by forming hypomorphic protein can activate RAD51. There is little data on whether different functional domains 1 and 2 genes modulate respo...

•Secondary, reversion mutations in BRCA genes can restore protein function.•Reversion mutations can underlie resistance to therapies such as PARP inhibitors.•Reversion mutations arise during the course of treatment.

The products of the BRCA breast cancer susceptibility genes have been implicated in cell cycle control and DNA repair. It has been suggested that mutations in the p53 gene are a necessary step in tumorigenesis in BRCA tumors. We tested samples from 402 breast cancer patients for germ-line BRCA2 and p53 mutations in tumors. p53 mutations are more frequent in BRCA2 mutation carriers than they are...