Genomic and Expression Profiling of Benign & Malignant Nerve Sheath Tumors in Neurofibromatosis Patients
Annual rept. 1 May 2005-30 Apr 2006
LELAND STANFORD JUNIOR UNIV STANFORD CA
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The goal of the study is to identify genes and pathways that are associated with the progression of neurofibroma to MPNST, and to identify potential therapeutic targets for MPNSTs. In the past year, to the existing 80 gene array data, we added an additional 23 tumor samples making to a total of 103 gene arrays. The analyses included 38 cases diagnosed as MPNSTs and 24 cases of neurofibromas. Our initial hierarchical clustering showed high degree of variability of MPNST cases. A centralized review of histology was performed of the 38 cases with the original diagnosis as MPNST, 14 cases were reclassified. In addition all MPNST and SS cases underwent RT-PCR for tX18. The misdiagnosed tumor cases were removed from the study, and a subsequent analysis and hierarchical clustering showed a much more interpretable result. The clustering of the nerve sheath tumors revealed a distinct expression signature for majority of benign and malignant tumor types. A subset of MPNSTs clustered along with SS. Using a large tissue microarray TMA with about 200 nerve sheath tumors we have identified a novel diagnostic marker TLE1 to distinguish SS from other sarcomas. The signaling pathways TGFB, JAK- STAT, MET were identified as being potentially involved in the malignant transformation. Array comparative genomic hybridization was performed on 28 tumor cases and copy number changes were assessed for each case.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research