DEREGULATED EXPRESSION OF PAX5 IN MEDULLOBLASTOMA

Medulloblastoma is a pediatric brain tumor originating in the human ce rebellum A collection of 23 medulloblastomas was analyzed for expressi on of the developmental control genes of the PAX and EN gene families by RNase protection and in situ hybridization, Of all nine PAX genes i nvestigated, only PAX5 and PAX6 were consistently expressed in most me dulloblastomas (70 and 78% of all cases, respectively), as were the ge nes EN1 (57%) and EN2 (78%), EN1, EN2, and PAX6 genes were also expres sed in normal cerebellar tissue, and their expression in medulloblasto ma is consistent with the hypothesis that this tumor originates in the external granular layer of the developing cerebellum, PAX5 transcript s were, however, not detected in the neonatal cerebellum, indicating t hat this gene is deregulated in medulloblastoma, In the desmoplastic v ariant of medulloblastoma, PAX5 expression was restricted to the retic ulin-producing proliferating tumor areas containing undifferentiated c ells; PAX5 was not expressed in the reticulin-free nonproliferating is lands undergoing neuronal differentiation. These data suggest that der egulated expression of PAX5 correlates positively with cell proliferat ion and inversely with neuronal differentiation in desmoplastic medull oblastoma.