Identifying and validating causal genetic alterations in human breast cancer.

An important mechanism for the activation of proto-oncogenes in human breast and other cancers is gene amplification, which results in gene overexpression at both the message and the protein levels. Recent studies have demonstrated that oncogenes rarely if ever become amplified in isolation, but rather are present on large amplicons that contain multiple genes. More detailed analysis of these amplicons has revealed the presence of many candidate breast cancer oncogenes. The broad goal of this issue of Breast Cancer Research and Treatment is to review the current state of our understanding of the causal role of defined genetic alterations that occur in human breast cancers, and to discuss the case for the mechanistic significance of several candidate oncogenes. As will be seen, these studies have revealed a remarkable genetic complexity and heterogeneity in human breast cancer that must be dissected in order to improve our mechanistic understanding of disease progression, and to develop effective new drugs against relevant molecular targets.