FREQUENCY OF P53 TUMOR-SUPPRESSOR GENE-MUTATIONS IN HUMAN PRIMARY BRAIN-TUMORS

MUTATIONS IN THE p53 tumor suppressor gene are the most common genetic alterations found in diverse types of human cancer, including the pri mary malignant brain tumor, glioblastoma multiforme. To estimate the f requency of p53 mutations in human brain tumors, we screened 120 human primary brain tumors (59 astrocytic; 61 nonastrocytic) by the polymer ase chain reaction-single-strand conformation polymorphism technique. Six astrocytic tumors (one anaplastic astrocytoma and five glioblastom a multiforme) were found to have putative p53 mutations. Direct sequen cing of polymerase chain reaction-amplified deoxyribonucleic acid from these six tumors confirmed the presence of different point mutations in the conserved regions of the p53 gene. Allelic losses on chromosome 17p were detected in four (67%) of the six tumors with p53 mutations. p53 mutations were not detected in any of the 61 nonastrocytic brain tumors. Also, polymerase chain reaction-single-strand conformation pol ymorphism analysis of 74 leukocyte deoxyribonucleic acid samples from patients with astrocytic and nonastrocytic brain tumors failed to dete ct any germ-line p53 mutations. We conclude from these findings that p 53 gene mutations in brain neoplasms are primarily limited to tumors o f astrocytic origin and that the p53 gene mutations in sporadic astroc ytomas are somatic in origin (i.e., nonprenatally determined).