Isolation of a Breast Cancer Tumor Suppressor Gene from Chromosome 3p

Loss of tumor suppressor genes by genetic mechanisms represent critical molecular events in the development and progression of breast cancer. One or more of these tumor suppressor genes likely resides on the short arm of chromosome 3 (3p) and appears to be involved in nearly 50% of breast cancers. We have identified a region in 3pl4 which undergoes recurrent homozygous deletion or rearrangement in breast cancer cell lines. A set of cloned DNA molecules spanning the target region has been established and a gene search is underway. In order to develop a functional tumor suppressor test of the 3pl4 and other target regions, we have begun to modify specific YACs with the Neomycin resistance gene that will permit their selective retention in mammalian cells. The identification of this homozygous deletion region is an exciting development that has resulted in a modification of the order for our Specific Aims.