Defective DNA damage responses in the nervous system can result in neurodegeneration or tumorigenesis. Despite the importance of DNA damage signalling, the neural function of many critical DNA repair factors is unclear. BRCA2 is necessary for homologous recombination repair of DNA and the prevention of diseases including Fanconi Anemia and cancer. We determined the role of BRCA2 during brain de...

A high mutation rate leading to tumor cell heterogeneity is a driver of malignancy in human cancers. Paradoxically, however, genomic instability can also render tumors vulnerable to therapeutic attack. Thus, targeting DNA repair may induce an intolerable level of DNA damage in tumor cells. BRCA2 mediates homologous recombination repair, and BRCA2 polymorphisms increase cancer risk. However, tum...

Although screening for large deletions or duplications of the BRCA1 gene is becoming a routine component of the molecular diagnosis of familial breast cancer, little is known about the occurrence of such rearrangements in the BRCA2 gene. Because of the high frequency of BRCA2 mutations in breast cancer families with at least one case of male breast cancer, we selected a cohort of 39 such famili...

Background BRCA2 c.68-7T>A has been demonstrated to cause aberrant splicing and is possibly pathogenic. The population prevalence of the variant is 0.2%, which higher than usual for pathogenic BRCA2 variants. The pathogenicity of the variant is discussed. Methods The outpatient genetic clinic at The Norwegian Radium Hospital, part of Oslo University Hospital, has invited breast cancer kindred...

In modern molecular genetics, epistasis analysis is a tool for probing the relationship between two genes and, hence, between the two genes’ products. In its broadest sense, an epistatic relationship exists when combinations of specific alleles of two or more genes generate a quantitative phenotype that differs from the simple addition of phenotypes associated with each individual allele. Many ...

BACKGROUND Breast cancer is one of the most common diseases affecting women. Inherited susceptibility genes, BRCA1 and BRCA2, are considered in breast, ovarian and other common cancers etiology. BRCA1 and BRCA2 genes have been identified that confer a high degree of breast cancer risk. OBJECTIVE Our study was performed to identify germline mutations in some exons of BRCA1 and BRCA2 genes for ...

CONTEXT Attempts to determine the clinical significance of BRCA1/2 mutations in ovarian cancer have produced conflicting results. OBJECTIVE To determine the relationships between BRCA1/2 deficiency (ie, mutation and promoter hypermethylation) and overall survival (OS), progression-free survival (PFS), chemotherapy response, and whole-exome mutation rate in ovarian cancer. DESIGN, SETTING, A...

In this issue, Hughes-Davies et al. describe a novel gene product, EMSY, which suppresses the transactivational activity of BRCA2. EMSY is located within an amplicon in sporadic breast and ovarian cancers, suggesting that its overexpression may mimic the effects of BRCA2 inactivation. The implications for BRCA2 function are discussed.

BRCA1, BRCA2, and PALB2 are key players in cellular tolerance to chemotherapeutic agents, including camptothecin, cisplatin, and PARP inhibitor. The N-terminal segment of BRCA2 interacts with PALB2, thus contributing to the formation of the BRCA1–PALB2–BRCA2 complex. To understand the role played by BRCA2 in this complex, we deleted its N-terminal segment and generated BRCA2 mutant cells. Altho...