NOVEL GENETIC ABERRATIONS IN PEDIATRIC AND ADULT ASTROCYTOMAS

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Although very few pediatric astrocytomas have been studied using cytogenetic or molecular genetic methods, it is known that adult astrocytomas often contain characteristic chromosome deletions and/or oncogene amplification. Because many high-grade adult astrocytomas are quite complex and heterogeneous genetically, it is likely that these tumors result from multiple oncogenetic events, acting in concert, that are necessary for full malignant progression. In a preliminary series that included 4 pediatric cases, we demonstrated clonal chromosome aberrations in 5 of 6 astrocytomas. An interesting secondary finding was that pediatric astrocytomas with high-grade histology appeared to have less genetic complexity and instability than that reported for similar adult tumors. We hypothesize that the relative genetic simplicity in pediatric cases will facilitate identification of novel genetic aberrations that might be relevant, as well, in adult astrocytomas. In the proposed studies, we will prospectively assess specific chromosome aberrations and genetic instability in pediatric and adult astrocytomas. The biologic relevance of these findings will be evaluated by correlation with histopathologic findings, overall survival, and Ki-67 proliferative index. Survival trends will be evaluated further by retrospective molecular cytogenetic analyses or frozen and/or paraffin-embedded astrocytoma specimens. The ultimate goal of these studies will be to fine map and characterize genetic aberrations which have clinical relevance in pediatric and adult astrocytomas.