Novel Therapies for Recurrent Meningiomas
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 9/30/06:
Meningiomas are common central nervous system tumors that originate from the coverings of the brain and spinal cord but very little is known about the genetic events responsible for their initiation or malignant progression. Recent studies suggest that this is a multi-step process, implying an accumulation of genetic mutation at specific loci. Dr. Carroll and her team are working to identify these genetic alterations in both benign meningiomas and those that have transformed into malignant tumors.
In addition to supporting Dr. Carroll’s powerful collaboration with Dr. Marco Giovannini, a world expert in the development of mouse models for benign tumors, BSF funding has allowed Dr. Carroll and her team to collect - from 15 patients - frozen samples of meningiomas that recurred as higher grade tumors. Samples were obtained from the initial surgery (grade I or grade II) and at the time of recurrence (grade II or III). Collected from the Brigham and Women’s Hospital (BWH) Tumor Bank and a number of hospitals across France, these tumor samples were examined by Dr. Jennifer Chan, a neuropathologist at BWH, to confirm the diagnosis and staging of the tumor.
Dr. Carroll’s team then isolated the DNA from the meningioma specimens and submitted the samples to the Harvard Partners Genetics and Genomics Center for hybridization to the Affymetrix single nucleotide polymorphism (SNP) arrays. With BSF funding, Dr. Carroll and her team were able to complete this significant undertaking, making their study the first to use SNP analysis to identify and validate in biological models the genomic alterations underlying progression and malignant transformation of human meningioma.
These newly released high density SNP arrays will allow Dr. Carroll and her team to detect for very small genetic aberrations. With the assistance of Dr. Peter Park, a biostatistician, statistical analysis has already begun. Moreover, with the help of Dr. Marco Giovannini, Dr. Carroll’s team has applied for a large collaborative grant from the Department of Defense, which would support their characterization of the newly identified genetic alterations in the meningioma.
Goals and Objectives
Supported by BSF funding, Dr. Carroll’s work in identifying new genetic alterations found in meningioma will lead to a better understanding of the molecular mechanisms involved in meningioma pathogenesis. The candidate genes identified in this study will facilitate the identification of novel diagnostic and prognostic markers for meningioma, which will guide the development of new therapeutic strategies.< Back
