RECENT DEVELOPMENTS IN THE MOLECULAR-GENETIC UNDERSTANDING OF BREAST-CANCER

The molecular genetic characterization of breast cancer has implicated or identified the involvement of at least 10 distinct gene alterations in the genesis or progression of this disease. The genes involved fall into three distinct classes, possibly reflecting their particular function in the tumorigenic process. First, there is a class of genes that is being amplified to various levels in clinically manifest breast cancer, most conspicuously c-neu, c-myc, and cyclin D1. Second, an as-yet unknown number of genes are targets for loss of heterozygosity or allelic imbalance events on a number of different chromosomes. Presumably, this reflects the presence of tumor suppressor genes located on chromosomes 3p, 6q, 16q, 17, and possibly a few additional chromosomes. Finally, at least three genes are implicated to confer heritable predisposition to breast cancer. These include the p53 oncogene on 17p, an as yet unknown gene on 17q, and at least one locus outside these regions. While a number of presently unknown genes will soon be identified and cloned, it is becoming evident from genetic mapping studies that the complexity of gene involvement in breast cancer has not yet seen its very limits. A comprehensive multidisciplinary molecular profiling of a large series of tumors of various histological subtypes may aid in understanding how the different genes may cooperate to cause breast cancer.