The Role of Cumulative Genetic Defects in NF1 Tumorigenesis

Abstract

The purpose of this work is to understand the genetic basis of tumor pathogenesis in neurofibromatosis type 1 (NE1) . This work will test the two-hit hypothesis in NE1 tumors (benign neurofibromas and MPNSTs), to assay for involvement of the TP53 gene in the various types of tumors, and to determine whether other loci contribute to the formation of NE1 tumors. This work is being done using human primary tumor samples, as well as using unique cell culture models derived from tumors and other sources of Schwann cells. The major accomplishments thus far include: strong evidence that the Schwann cell is genetically aberrant in neurofibromas and can be successfully enriched in culture (i.e., the clonal origin), that multiple genetic defects occur in many plexiform neurofibromas but that there is less evidence of large genetic rearrangements in dermal neurofibromas, that the two-hit hypothesis is supported in at least most tumors by genetic and protein assays, and that the TP53 gene is only abnormal in MPNSTs (the malignant tumors).

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 1999
Accession Number
ADA385685

Entities

People

  • Margaret Wallace

Organizations

  • University of Florida

Tags

DTIC Thesaurus Topics

  • Brain
  • Cancer
  • Cell Physiological Processes
  • Cells
  • Culture Techniques
  • Genetics
  • Health Services
  • Medical Personnel
  • Neoplasms
  • Neuromuscular Diseases
  • Neurosciences
  • Programmed Cell Death

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and Cellular Biology
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology