ABSTRACT
In the decade since the discovery of the BRCA1 and BRCA2 genes, our understanding of their function has grown tremendously, albeit, slowly. We have advanced from knowing
virtually nothing about these genes (other than they were cancer risk factors) to a point
where new classes of anti-tumor drugs are being tested based on knowledge of the
BRCA1 and BRCA2 “pathway.” The cloning of these genes was heralded as a great breakthrough in breast cancer research. In retrospect, identifying the genes was the simple
part. It took 10 years because the technology and infrastructure that support positional
cloning were not yet mature. Why did it require another decade to develop an
understanding of the function of these genes? Much of the explanation can be placed on
our difficulty is fleshing out new aspects of biology when handed genes of unknown
function that lack sequence similarity to known genes. Such was the case for BRCA1 and BRCA2. Their amino acid sequence bore little resemblance to any previously cloned genes. Prior to their cloning, data from tumors suggested that both BRCA1 and BRCA2 are tumor suppressor genes. Having the genes in hand has allowed those in the field to
investigate all aspects of BRCA1 and BRCA2 biology. This chapter is not intended to be an exhaustive review of the field; rather, our intent was to focus on those advances most
directly relevant to the clinician.
