About 1 in every 10 women will suffer from breast cancer at some point in their lives, and so the identification of breast cancer susceptibility genes BRCA1 and BRCA2 in 1994-95 has excited much interest from researchers in the scientific and medical communities. My review paper was an attempt to pull together many different strands of research into a coherent model for the function of the BRCA1 and BRCA2 proteins, and their role in carcinogenesis, at a time when the field was progressing rapidly. Perhaps that is why it is highly cited.

It argues that the biological functions of the BRCA proteins in the cellular response to DNA damage account for their role as tumor suppressors, that BRCA1 and BRCA2 have distinct functions in the response, and that the evolution of cancers from BRCA-deficient cells is shaped by the requirement for certain secondary genetic events that suppress the deleterious effects of BRCA inactivation on cell viability.

Whilst the paper obviously overviews the work of many colleagues in the field, I drew several key elements from the work of my own laboratory on BRCA2 during the 4 years preceding this paper. We were led to do this research initially because of our interest in how dividing immature cells in the immune system could co-ordinate cell division with the creation and repair of DNA breaks during V(D)J recombination.

About half of all inherited breast cancer is due to mutations in either one of two genes, BRCA1 or BRCA2. This paper tries to explain how mutations in BRCA1 or BRCA2 could cause cancer, using information from research carried out by many different laboratories.

Professor Ashok R. Venkitaraman
Department of Oncology and The Medical Research Council Cancer Cell Unit
University of Cambridge, CR UK