Transcriptional Repression as a Mechanism of BRCA-1 Inactivation
Abstract
The basic hypothesis of this project is that aberrant cytosine methylation of the BRCA-1 CpG island promoter is a mechanism of BRCA-1 gene inactivation in sporadic human breast cancer. To test this hypothesis, archived frozen human breast cancer specimens were analyzed. Quantitative RT/PCR analysis was used to determine BRCA-1 gene expression levels in breast cancer specimens and cytosine methylation status of the BRCA-1 CpG island promoter was determined using the high resolution bisulfite sequencing technique. We have analyzed 21 axillary node negative breast cancer specimens. Results show a greater than 2-fold decrease in BRCA-l mRNA levels in 4 of 2l breast cancer specimens (19%). Of these samples, the three with the lowest levels of BRCA-l expression also showed aberrant methylation of the BRCA-l core promoter (CpG island). Aberrant methylation of BRCA-l core promoter was not detected in any breast cancer samples that had <2-fold decrease in BRCA 1 expression. These results suggest that aberrant methylation of the BRCA-1 CpG island promoter is associated with down regulation of BRCA-l gene in a subset of human breast cancers, and that BRCA-1 methylation patterns may be useful as a biomarker of disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA389578
Entities
People
- Bernard Futscher
Organizations
- University of Arizona