Principal Investigator:
Dr. Rona Carroll, Ph.D., of the Harvard Medical School and the Brigham and Women’s Hospital
Project Summary and Update as of 9/30/05:
Although meningiomas are common central nervous system tumors, very little is known about the genetic events responsible for their initiation or malignant progression. The lack of a viable animal model is a rate limiting step to advancing the understanding of the biology of meningiomas. Dr. Carroll and her team have been working with Marco Giovannini and Michel Kalamarides in Paris, France. The French group created the first transgenic mouse model of meningioma and have concluded that mutation in the Nurofibromatosis Type 2 (Nf2) gene is an early step in meningioma development. Through the use of magnetic resonance imaging done in Boston, Dr. Carroll’s team determined the timing of meningioma initiation and progression. Although the specific gene mutations in mice cause the increase in the frequency of meningioma development, they do not seem sufficient to promote meningioma malignancy. While this initial model can be used to screen new therapeutics for meningioma treatment, there is still the need to identify other genetic abnormalities in meningiomas involved in meningioma initiation, growth and progression and use these findings to subsequently develop new mouse models.
Goals and Objectives - New Directions:
The results from the first model studies suggest that there is a mutli-step process involved, implying an accumulation of genetic mutations at specific loci. Therefore, this project is now moving in a new direction to identify new genes underlying meningiomagenesis and tumor progression. The goal is to identify these genetic alternations in both benign meningiomas and those that have progressed to a more malignant phenotype. The identification of these genetic alterations will lead to the development of new therapeutic targets. Integrated transcriptional profiling and LOH analysis, using human SNP (Single Nucleotide Polymorphisms) microarray technology will be employed to meet these goals. SNP analysis is a method of genotyping to identify genes that may be instrumental in meningioma initiation and progression. Dr. Carroll will then engineer new mouse models of meningioma using those genes identified by SNP analysis.
Project History:
Start Date: October 2002
End Date: September 2006 (project may be extended based on findings)
BSF Funding through 9/30/05: $236,918
BSF Current Fiscal Year Funding: $126,155
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