Genetic Evaluation of Peripheral Nerve Sheath Tumors in Neurofibromatosis Type I

Abstract

The goal of this research project was to identify molecular changes associated with the progression of peripheral nerve sheath tumors in neurofibromatosis type 1 (NF1). Archival and prospectively acquired plexiform neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) were collected and evaluated by immunohistochemical stains and genetic analyses. Tumor heterogeneity has been assessed by both methodologies. The level of ras signal transduction activity in frozen tumor specimens was estimated by ras-GTP/ras-GDP ratios - A number of archival specimens in paraffin blocks have been evaluated, whereas a relatively small number of MPNSTs have been collected for complete analysis. Immunohistochemical stains have been developed to distinguish -high-grade versus low-grade MPNSTs and plexiform neurofibromas. The genome of plexiform neurofibromas is relatively stable, compared to the random genomic imbalances identified in low- and high-grade MPNSTs. There is minimal tumor heterogeneity in the plexiform neurofibromas, whereas there is increased tumor heterogeneity in MPNSTs. Ratios of ras-GTP to ras-GDP, in a subset of peripheral nerve sheath tumors, did not correlate well with level of malignancy.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2003
Accession Number
ADA421066

Entities

People

  • David H. Viskochil

Organizations

  • University of Utah

Tags

DTIC Thesaurus Topics

  • Arteries
  • Cell Physiological Processes
  • Chemical Synthesis
  • Chemistry
  • Genetics
  • Health Services
  • Medical Personnel
  • Neuromuscular Diseases
  • Oncology
  • Peripheral Nervous System

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.
  • Neuroscience

Technology Areas

  • Biotechnology