CONSTITUTIONAL P53 MUTATIONS ASSOCIATED WITH BRAIN-TUMORS IN YOUNG-ADULTS

Identification of patients at risk for developing brain tumors is impo rtant for the development of preventative strategies. Because individu als with germline p53 mutations may be at increased risk, we examined DNA from brain tumor-derived cell lines and malignant and normal nervo us system tissue for p53 gene mutations using the single strand confor mation polymorphism assay and direct sequencing of polymerase chain re action-amplified DNA. We found mutations in the p53 gene in eight of 2 2 adult glioma tissue specimens and germline mutations in two of these eight patients. In contrast, mutation of the p53 gene was not detecta ble in either 16 glial tumors occurring in children, glial tumor tissu e from three unrelated glioblastoma multiforme patients with a familia l history of cancer, or in benign meningiomas. One constitutional p53 mutation was a G to T transversion at codon 154, and the second was a C to T transition at codon 256. Both patients with germline mutations developed glioblastoma multiforme before the age of 31, although the m edian age for glioma patients is above 50. These findings suggest that p53 germline mutations may identify a subset of young adults predispo sed to the development of high-grade astrocytic tumors.