Clinical and Molecular Consequences of NF1 Microdeletion
Abstract
Skin neurofibromas are the most common tumors of patients with neurofibromatosis type 1 (NF1), yet we know very little about how they develop. We are studying subjects with microdeletions because they are predisposed to large numbers of neurofibromas. We propose that deletion of NF1 gene and at least one of the 15 adjacent genes favors the development of skin neurofibromas, and probably other NF1-related tumors. We are evaluating NF1 subjects to identify those with deletions and determine when and what kind of tumors and other clinical features they develop. We have developed rapid and sensitive assays for the detection and mapping of NF1 microdeletions. Using these assays, we screened 242 patients and identified 56 carriers of the recurrent 1.4Mb NF1 microdeletions and 16 carriers of novel deletions. Clinical evaluation of these patients, along with age/sex matched NF1 patients that are not NF1 deletion carriers, i& in progress to delineate the clinical manifestations most prevalent in deletion patients. We have collected tumors from NF1 microdeletion carriers, which are now being examined for mutations and genomic instability. We began a new collaboration and generated preliminary data that identified an apparent new function of neurofibromin as a caspase target. Since this work is outside the scope of this grant, we have submitted a new application for investigating the role of caspase in NF1 disease and tumorigenesis. Therefore, our progress on genotype/phenotype correlations in carriers of NF1 microdeletions, along with our new work identifying neurofibromin as a caspase target, will provide clinically applicable information for patient diagnosis and management and basic knowledge about neurofibromin function in disease pathogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2005
- Accession Number
- ADA437875
Entities
People
- Karen Stephens
Organizations
- University of Washington