The Role of Cumulative Genetic Defects in NF1 Tumorigenesis
Abstract
The purpose of this work is to study the genetic basis of tumor pathogenesis in neurofibromatosis type 1 (NFl) . This work tests the two-hit hypothesis in NFl tumors (benign neurofibromas and MPNSTs), the involvement of the TP53 gene in the tumors, and whether other loci contribute to the tumor formation. A large set of human primary tumor samples has been collected, with development of cell culture models from these tumors. One accomplishment has been discovery that the two-hit mechanism operates in at least a large proportion of neurofibromas, and that there is a genetically abnormal Schwann cell component in these tumors. Both germline and somatic NFl mutations have been found, and we have evidence for somatic isodisomy as the mechanism for loss of heterozygosity. The TP53 gene has been found to be implicated only in the malignant tumors. The NF2 gene has allelic loss in some MPNSTs and plexiform tumors, with testing in dermal tumors and schwannomas underway. Substantial data from broader surveys of other genes (differential display, oDNA array, mutation screening) are under analysis. These data are important in the development of rational therapies to prevent or halt progression of neurofibroma and MPNST growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA401167
Entities
People
- Margaret Wallace
Organizations
- University of Florida