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 . In an ongoing multiinstitutional 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 CieneChip method, SSCP, and sequencing. 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 is examining 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, and 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. P53 mutation analysis upon the study samples is underway. Implementation of the yeast-based functional assay for assessing the effect of specific p53 mutations has been successful with altered transactivation function found in mutations from neoadjuvantly treated patients.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2005
Accession Number
ADA443992

Entities

People

  • Brian Popko
  • Chad Livasy
  • Charles M. Perou
  • Kathy C. Dorsey
  • Laura Esserman
  • Lisa A Carey
  • Lynn Dressler
  • Michael Resnick
  • Michael Schell
  • Scott Drouin

Organizations

  • University of North Carolina at Chapel Hill

Tags

DTIC Thesaurus Topics

  • Acids
  • African Americans
  • Amino Acids
  • Amplification
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cells
  • Chemotherapy
  • Gene Expression
  • Health Services
  • Neoplasms
  • Nucleic Acids
  • Public Health
  • Teamwork
  • Test And Evaluation
  • Therapy

Readers

  • Molecular and genetic basis of cancer.
  • Trauma or Military Medicine