Identifying and Isolating Breast Cancer Associated Genes on Chromosome 11.

Abstract : There is a region on human chromosome ii at pl 5.5 that has been associated with the breast cancer phenotype. These results were obtained by loss of heterozygosity (LOM) studies in breast tumors. Metastasis and poor outcome are the cancer phenotypes associated with lip' 5.5. Since breast cancer patients usually do not die as a result of the primary tumor, but from the progression to a metastatic phenotype, we have embarked on a study to identify% the gene(s) responsible on lip15.5. We have constructed a detailed physical map across the region, participated in sequencing the region, generated a transcript map across the region and have begun to access the genes in this region as candidates for tumor suppressor genes. The candidate region has been reduced to 400 kb and contains about 4-6 potential genes. We have cloned the region and the molecular characterization has begun. Interestingly, the 11p15.5 .5 region has been shown to be located in an imprinted domain. We have evidence to suggest preferential 11pl 5.5 maternal loss in breast tumors suggesting that breast cancer in this region has an imprinting component. We have cloned the homologous imprinted region from the mouse and are testing for imprinted expression in fetal and adult tissues including mammary gland.