Monoclonality and Genetic Instability in Premalignant Breast Tissue
Abstract
By the time a cancer is detected, its tumor cells already exhibit myriad genetic abnormalities. To gain a better understanding of genetic events that occur early in breast carcinogenesis, this research' examines genetic abnormalities in: (1) histologically normal tissue from women at low, medium or high breast cancer risk, using a variety of archival breast tissues; and (2) in synchronously occuring putative precursor lesions, including normal-appearing epithelium, simple and atypical proliferative lesions and carcinomas themselves. Each specimen is microdissected, its DNA examined using a panel of selected microsatellite markers and evidence of clonal abnormalities sought, in particular loss of heterozygosity (LOH) and microsatellite instability (MI). Investigation of the project's first goal is generating data regarding the timing and sites of early genetic abnormalities. These data raise the possibility that a field defect exists in curtain breast tissue. Investigation of the second goal is uncovering that a variety of clonal relationships exist between multiple synchronous putative precursors. These studies should identify important sites of genetic abnormalities in early breast cancer precursors, and begin to outline the sequence of acquired genetic abnormalities needed for precursor lesions to evolve into full-blown malignancies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2000
- Accession Number
- ADB262448
Entities
People
- Carol L. Rosenberg
Organizations
- Boston University