RARE OCCURRENCE OF INACTIVATING P53 GENE-MUTATIONS IN PRIMARY NON-ASTROCYTIC TUMORS OF THE CENTRAL-NERVOUS-SYSTEM - REAPPRAISAL BY YEAST FUNCTIONAL ASSAY

While it is established that p53 mutation plays a critical role in the carcinogenesis of astrocytic brain tumors, its role remains to be cla rified for other types of tumors in the central nervous system (CNS). Using a yeast-based assay which tests the ability of human p53 to acti vate transcription, we analyzed p53 mutations in 85 non-astrocytic CNS tumors, including 4 benign neuronal tumors (3 central neurocytomas an d 1 pineocytoma), 12 primitive neuroectodermal tumors, 14 germ cell tu mors (7 germinomas, 7 non-germinomatous tumors), 4 craniopharyngiomas, 14 ependymomas, 22 schwannomas, 10 primary brain lymphomas in immunoc ompetent patients, and 5 bone tumors of the skull. The only tumors fou nd to contain p53 mutations were 3 malignant lymphomas. The presence o f mutations in these cases was confirmed by DNA sequencing. Given the high accuracy and sensitivity of the yeast assay and previous negative results using conventional techniques, this indicates that p53 mutati on is a rare event in non-astrocytic CNS tumor types examined here.