P53 Mutation Analysis to Predict Tumor Response in Patients Undergoing Neoadjuvant Treatment for Locally Advanced Breast Cancer
Abstract
Studies suggest that p53 mediates responsiveness to chemotherapy. The development of p53 GeneChip technology has made high-throughput mutation analysis more feasible. In an ongoing multi-institutional prospective trial that is not supported by this award, breast cancer patients receiving neoadjuvant chemotherapy have serial response assessments and tumor sampling for research purposes. The project that is supported by this award involves analyzing the banked tumor specimens for p53 mutations using the GeneChip method. We hypothesize that p53 status of the primary tumor will predict response to anthracycline-based and taxane-based chemotherapy given at different times in the same patient. A yeast-based functional assay will examine the impact of specific p53 mutations upon transactivation function. Progress to date includes optimizing the GeneChip method of p53 mutation analysis for core biopsy specimens, successful scaling down of the DNA requirements for such assays allowing evaluation of small tumor biopsy samples, optimizing methods for p53 amplification within 1-2 large fragments so that SSCP and sequencing analysis will be feasible despite the small amount of DNA available, initiating p53 mutation analysis upon the study samples, and adaptation and successful implementation of the yeast-based functional assay for assessing the effect of specific p53 mutations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA433971
Entities
People
- Lisa A Carey
Organizations
- University of North Carolina at Chapel Hill