Monoclonality and Genetic Instability in Premalignant Breast Cancer
Abstract
Breast cancer probably develops as multiple genetic abnormalities accumulate, but the timing and nature of the earliest steps in this progression remain unknown. Proliferative breast lesions, considered benign but associated with increased breast cancer risk, were recently shown to contain clona 1 genetic abnormalities. Therefore, we hypothesized that clonal genetic abnormalities might be detectable before any phenotypic abnormalities develop: i.e., in microscopically normal breast tissue. We examined DNA from 95 normal-appearing ducts or terminalductal-lobular units (TDLU) from 20 individuals with varying breast cancer risk: those undergoing reduction mammoplasty, those with proliferative lesions, and those already with breast cancer. Using 9 microsatellite markers, we looked for genetic instability, 0 allele imbalance, most likely loss of heterozygosity (LOH). We found genetically abnormal clones in 21/95 (22%) of seemingly normal samples from 10/20 (50%) women from all 3 risk groups. In women under age 50, trends towards increased rates of abnormalities were noted with increased cancer risk. Abnormalities were more likely to be at sites of known or postulated tumor suppressor genes than at random or neutral loci.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1999
- Accession Number
- ADA369256
Entities
People
- Carol L. Rosenberg
Organizations
- Boston University