BRCA2 gene

The BRCA2 gene (BRCA2 stands for "Breast Cancer Type 2 Susceptibility Protein") is a protein-coding gene located on chromosome 13q12.3.

Both BRCA1 and BRCA2 are involved in maintaining genome stability, particularly in the homologous recombination pathway for double-stranded DNA repair. The largest exon in both genes is exon 11, which harbors the most important and common mutations in breast cancer patients.

The encoded BRCA2 protein contains multiple copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to RAD51 recombinase, which is active in DNA repair. BRCA2 is considered a tumor suppressor gene because tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele.

Germline BRCA2 mutations have become a hallmark of hereditary breast and ovarian cancer. Variants that have been shown to affect the function of the protein have been shown to increase the risk of these cancers, as well as prostate and pancreatic cancers. These findings have led to the increasing popularity of genetic testing for risk assessment in healthy individuals. Recent studies in ovarian cancer have also shown that BRCA mutation status can predict response to treatment. A number of studies examining BRCA mutation status have shown improved response to platinum agents, and more recently this has led to FDA approval of PARP inhibitors for BRCA-positive ovarian cancers. These studies have led the Society of Gynecologic Oncology to recommend BRCA germline testing in all patients diagnosed with ovarian cancer.

Diseases associated with BRCA2 include Fanconi anemia, complementation group D1, and breast cancer.

Inherited mutations in BRCA1 and this gene, BRCA2, lead to an increased lifetime risk of breast or ovarian cancer.

1. Bhatia V et al.(2014), Barroso SI, García-Rubio ML, Tumini E, Herrera-Moyano E, Aguilera A. BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2. Nature 511:362-365.