Identification of Rad51 alteration in patients with bilateral breast cancer

The human Rad51 gene, HsRAD51, is a homolog of RecA of Escherichia coli and functions in recombination and DNA repair. BRCA1 and BRCA2 proteins form a complex with Rad51, and these genes are thought to participate in a common DNA damage response pathway associated with the activation of homologous r ecombination and double-strand break repair. Additionally, we have shown th at the pattern of northern blot analysis of the Rad51 gene is closely simil ar to those of the BRCA1 and BRCA2 genes. It is therefore possible that alt erations of the Rad51 gene may be involved in the development of hereditary breast cancer. To investigate this possibility, we screened Japanese patie nts with hereditary breast cancer for Rad51 mutations and found a single al teration in exon 6, This was determined to be present in the germline in tw o patients with bilateral breast cancer, one with synchronous bilateral bre ast cancer and the other with synchronous bilateral multiple breast cancer. In both patients, blood DNAs showed a G-to-A transition in the second nucl eotide of codon 150. which results in the substitution of glutamine for arg inine. As this alteration was not present in any patients with breast or co lon cancer examined, we assume that this missense alteration is likely to b e a disease-causing mutation.