Expected Results and Relevance
Pilocytic astrocytoma (PA) is the most common central nervous system tumor in the pediatric population. PA is typically benign, indolent, and slow growing. In a small subset of patients, however, this tumor exhibits aggressive growth and carries a poor prognosis. We previously characterized these unique tumors, both clinically and histologically. This neoplasm has been termed pilomyxoid astrocytoma (PMA) based on its microscopic appearance. While tumors have traditionally been categorized on the basis of their histology, the unique pattern of cancer cells under the microscope is insufficient to reflect the complex molecular events that drive the neoplastic process. Therefore, a critical challenge facing neuro-oncology is the development of tumor classifications that reflect the underlying molecular and genetic abnormalities. This protocol, termed molecular profiling, holds tremendous potential for the future treatment of cancer. The development of inhibitors targeted to specific genetic mutations or pathways represents an important new approach to cancer therapy. Advances in molecular profiling of tumors can help pinpoint new targets for drug development and identify subsets of individuals that will maximally benefit from specific treatments.
Our expected results are twofold. First, by investigating mutations that are known to occur in PA as well as those that tend to occur in more aggressive neoplasms, we expect to find genetic differences between PA and PMA as well as genetic similarities between PMA and more aggressive neoplasms. This specific pattern of genetic alterations seen in PMA should further elucidate the aggressive biologic behavior exhibited by PMA. Second, upon identifying genetic mutations unique to PMA we aim to investigate alterations in both gene and protein expression. This would help identify products of the downstream pathway that may be involved in the cell cycle, apoptosis, and the ability of cancerous cells to metastasize.