Genetic Damage Caused by ALU Repeats in Breast Cancer
Abstract
Retrotransposition by Alu and Ll elements represents 0.2% of all human genetic disease and is likely to be stimulated in tumors. We hypothesize that retrotransposition may be stimulated sufficiently in breast tumors to allow these insertions to make a significant contribution to mutations that may lead to breast cancer progression. Our evolutionary analysis led us to define specific diagnostic sequence differences that differentiate the most recent 2000 Alu inserts from the 1,000,000 older elements. We have developed an anchored PCR strategy that allows us to display' small subsets of these recent Alti elements on a gel. We will use this approach to look for de novo Alu insertions in breast tumors. We have recently refined the evolutionary analysis to allow us to detect over one third of all Alu insertions in three subsets that consist of a total of about 150 elements. Each of these subsets can be readily assayed individually. We have also used a retrotransposition reporter system to demonstrate that p53 mutations greatly enhance retrotransposition rates. Because p53 mutations are among the most common breast cancer mutations, this strongly supports our hypothesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA387783
Entities
People
- Prescott Deininger
Organizations
- Tulane University of Louisiana