Technical Details:
The technology concerns the identification of second-site suppressor mutations that can act as Aglobal suppressors@ to overcome the deleterious effects of common p53 cancer mutations responsible for more than 50% of all cancers. Such suppressor mutations restore function to mutant (tumor-derived) p53 molecules. These mutations were identified by using a p53 yeast assay that assesses p53 function by its ability to bind to a p53 DNA binding site and transactivate the downstream reporter gene URA3 and validated in mammalian cell culture models. Using PCR mutagenesis and gap repair in yeast, several intragenic missense suppressor mutations were discovered that reverse the effects of specific p53 cancer mutations. The need for more efficacious cancer treatment is overwhelming as one of five Americans will develop cancer. The clinical relevance of this technology is significant as the presence of wild-type tumor suppressor gene p53 in human cancers correlates well with successful anti-cancer therapy and is expected to improve treatment outcomes. The economic relevance is also significant as the expenditure on cancer treatment often reaches 3 to 6% of the gross national product in developed countries
