Genetic Factors That Affect Tumorigenesis in NF1
Abstract
Neurofibromatosis type 1 predisposes to the growth of both benign and malignant tumors. Genetic factors, in addition to inactivation of the NF1 gene itself, clearly play a role in tumor development. Our research is focused on identifying specific DNA sequences and genetic mechanisms important in the development of cutaneous neurofibromas. We are analyzing NF1 microdeletions, which are associated with an early onset, and subsequent heavy burden, of cutaneous neurofibromas. We identified recombination hotspots where breakpoints in ^75% of patients with NF1 microdeletions occur and developed assays that detect microdeletions in a patient blood sample. Near the recombination hotspots where microdeletions occur, we identified unique sequence elements that may mediate recombination at these sites and make some chromosomes susceptible to NF1 microdeletion. Unexpectedly, we found that NF1 microdeletions that arise in a somatic cell during early embryogenesis occur at different sites. An understanding of how NF1 microdeletions occur, whether some individuals are more susceptible, and why they potentiate the development of neurofibromas is important for patient care, genetic counseling, and the design of effective pharmacological intervention strategies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2001
- Accession Number
- ADA400492
Entities
People
- Karen G. Stephens
Organizations
- University of Washington