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

Loss of tumor suppressor genes TSGs represent critical molecular events in the development and progression of breast cancer. Based on loss of heterozygosity LOH studies as well as direct cytogenetic studies of breast tumors, one or more TSGs likely resides on the short arm of chromosome 3 3p and appears to be involved in nearly 50 of breast cancers. Four distinct regions within 3p P12, P14, P21 PROXIMAL AND P21 DISTAL undergo recurrent deletions in human carcinomas and are the most likely sites for a breast cancer TSG. In our previous Progress Reports and publications, we demonstrated recurrent homozygous deletion or rearrangement in breast cancer cell lines involving 3p14. The critical region was cloned and sequenced which led to the identification of several putative exons. We determined that 3p14 is subject to a high degree of genomic instability which is ongoing in some cases. We have also made substantial progress in evaluating other 3p regions for involvement in breast cancer, as originally proposed. This has included the 3p21.31 and 3p21.33 homozgyous deletion regions as well as the interval between. In addition, we have discovered a novel patched-related gene which resides in a region of frequent amplification in breast tumors.