Genomic and Expression Profiling of Benign and Malignant Nerve Sheath Tumors in Neurofibromatosis Patients

Abstract

The goal of the study is to identify genes that will serve as molecular markers for progression of neurofibroma to MPNST, and to identify potential therapeutic targets. Gene expression profiling was performed on 26 cases of MPNSTs, 23 schwannomas, 20 neurofibromas and II synovial sarcomas. By using unsupervised hierarchical clustering most tumors were grouped together according to tumor type. Further analysis suggested that a major trend in transformation from neurofibroma towards MPNST is accompanied by the loss of gene expression in a large number of genes, rather than widespread de novo expression of genes upon transformation. Subsequent analyses using Significance Analysis of Microarrays (SAM) identified genes that differentiate various nerve sheath tumors. The analysis also indicated new subtypes of MPNSTs. Expression of genes associated with TFGB signaling in majority of neurofibromas but not in MPNST suggest that TGFB signaling is one of the key regulatory pathways in neurofibromas. A large tissue microarray (TMA) was made containing 200 nerve sheath tumors and is being tested by IHC and ISH markers.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2005
Accession Number
ADA438988

Entities

People

  • Brian Rubin
  • Matt J. Van De Rijn
  • Torsten Neilsen

Organizations

  • Stanford University

Tags

DTIC Thesaurus Topics

  • Biological Factors
  • Biomedical And Dental Materials
  • Carrier Proteins
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Cytoskeleton
  • Dna Microarrays
  • Growth Factors
  • Neoplasms
  • Neurofibromatosis
  • Peptide Growth Factors
  • Peptides
  • Peripheral Nervous System
  • Polymeric Films
  • Proteins
  • Tissues

Fields of Study

  • Biology

Readers

  • Molecular and Cellular Biology
  • Molecular and genetic basis of cancer.
  • Oncology and Biomarker-Based Cancer Detection.