Identification of BRCA1 and 2 Other Tumor Suppressor Genes on Chromosome 17 Through Positional Cloning

摘要

The overall goal of this project is to identify genes involved with the development and progression of breast cancer. This goal has remained unchanged since the start of the project, however the discovery of BRCA1 in 1994 together with technological advances in gene expression profiling has influenced our strategy to achieve this goal. In the early part of the project our search for tumor suppressor genes was directed by genetic or LOH mapping strategies followed by positional cloning of candidate genes. As we proposed in our revised statement of work (SOW), we have now focused our efforts entirely on microarray-based comparisons to identify breast cancer related genes. Our laboratory has gained access to this technology through collaboration with Molecular Dynamics and now we have established microarray spotting and scanning systems with over 40,000 minimally redundant sequence-verified human cDNA clones. Once candidate genes have been identified, they will be further characterized using a retroviral-based conditional expression system to assess changes in characteristics pertaining to morphology and growth rate by culturing human breast epithelial cells in an extracellular matrix.