Genomic and Epigenomic Characterization of NF1-Related Spectrum of Peripheral Nerve Sheath Tumors
Abstract
Neurofibromatosis Type 1 (NF1) is a hereditary disease that affects 1 in 3,500 individuals and results in the development of multiple tumors outside the skull that are called peripheral nerve sheath tumors (PNSTs). Some of these tumors are benign, while some are malignant. Although a large number of these PNST tumors are benign, they cause significant morbidity such as physical disfigurement, neurological defects, and pain. Approximately 10% of the benign PNSTs become malignant tumors that are called malignant peripheral nerve sheath tumors (MPNSTs). Recently, a novel method of diagnosis was proposed by a pathologist for a specific subtype of neurofibroma called atypical neurofibromatosis neoplasm of unknown biological significance (ANNUBP), which is characterized by aggressive features. This subtype is likely to become a malignant tumor and pose a major clinical challenge, as the biological reason for this transformation into a malignant tumor is not known. Preliminary data from our laboratory has uncovered specific modifications in the DNA of a majority of ANNUBPs, which is a finding not observed in other benign neurofibroma types. We hypothesize that ANNUBPs have specific genomic features that increase the risk of malignant transformation. The goal of our research proposal is to characterize the molecular alterations in both malignant and benign PNSTs and identify potential therapeutic methods. We will take advantage of our institutional brain tumor bank that harbors more than 200 PNSTs (250 benign and 50 malignant) with complete clinical data associated with the patients in order to perform technically advanced genomic analysis of PNSTs. This will allow future research to target the critical mutated genes with specific drugs that may be already available for other tumor types. Ultimately, any new findings will be tested in cells and mice with PNSTs to confirm their functional role in tumor development and malignancy. The genomic analysis proposed in this study would establish distinct signatures in PNSTs that would potentially predict malignant transformation and enable identification of patient-specific therapies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910779
Entities
People
- Gelareh Zadeh
Organizations
- United States Army
- University Health Network