MOLECULAR BIOMARKERS IN THE CLASSIFICATION OF GLIMOAS

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The goals of this study are to identify and evaluate molecular markers useful in the classification and grading of gliomas. The intended projects, as listed in the Specific Aims, were selected so as to address problems in tumor classification whose resolution, we believe, will significantly improve the diagnosis, and therefore treatment, of patients with brain tumors. These issues include: (1) the details and diagnostic specificity of molecular changes in spectrum of pilocystic astrocytomas arising in both patients with neurofibromatosis 1 and in the general population without a recognized genetic predisposition to this common pediatric neoplasm, (2) the presence or absence of similar molecular changes in sporadic non-pilocystic tumors (high grade fibrillary astrocytic tumors and oligodendrogliomas) and how these might be related to tumor classification, (3) the prognostic utility in higher grade astrocytic neoplasms of the cycling cell marker Ki-67 and amplification of the epidermal growth factor receptor gene, (4) the genomic abnormalities associated with tumor progression in fibrillary astrocytic and oligodendroglial neoplasms, and how these changes can be used in tumor grading and prognosis, and (5) the determination of tumor extent (staging) of the untreated glioblastoma by unambiguous molecular methods. The proposed research benefits from strong interactions with the multicenter CNS Consortium New Approaches to Brain Tumor Therapy (NABTT). NABTT will provide ready access to rare tissue resources and the extensive clinical and scientific data from a large collection of patients diagnosed with primary gliomas required for our analyses. Our molecular findings derived from PCR-based highly efficient methods will be correlated with clinical parameters including the response to specific NABTT initiated treatments. Close interactions between our Cooperative Glioma Network multidisciplinary research team and the NABTT will significantly extend the resources of both studies. These studies will improve our knowledge of the molecular alterations of these tumors and provide diagnostic markers that can be correlated with outcome. Moreover, these data will provide the basis for future studies on the pathophysiologic mechanisms of gliomas and lead to new approaches to treatment.