Alterations of the TP53 Gene in Human (¿liornas1

i .lini tumors of all grades and histolÃ3gica! types from 72 adults and 48 children were analyzed for mutations of the TP53 gene, loss of heterozygosity (LOH) for I7p, and accumulation of TP53 protein to determine whether the incidence and type of TP53 alterations differ among tumors of different histolÃ3gica! type and between tumors from adults and chil dren. These tumors were also evaluated for LOH for chromosome 10 and for amplification of the epidermal growth factor receptor, C-MYC, NMYC, GLI, platelet-derived growth factor receptor-a, and murine double minute 2 genes to determine the patterns of molecular alterations involved in the progression of these neoplasms. Seventeen of the 120 tumors con tained mutations of the TP5.ÃŒgene. One of the tumors with TP5.1 gene mutation was from one of the 48 patients less than 18 years of age. Twelve of the 17 tumors with mutations occurred among the 27 patients in the 18—15-yearage group, while 4 tumors with mutations were among the 45 patients more than 45 years old. There was also an increased incidence of TP53 mutation in patients with anaplastic astrocytoma histology. How ever, no significant association between presence of TP53 mutation and patient survival was observed. These studies demonstrate that TP53 gene mutations are a common mechanism for glial cell neoplasms in the 1845-year age group but are unrelated to progression and advanced histo lÃ3gica! grade. LOH for chromosome 10 and gene amplification, however, occurring in 82 and 40%, respectively, of glioblastoma multiforme, whether seen alone or along with TP53 gene alterations, are related to advanced histolÃ3gica! grade of the tumor. In childhood gliomas, in con trast, TP53 gene alterations, LOH for 17p and lOq, and gene amplification are uncommon in tumors of all grades, suggesting that presently unknown mechanisms are responsible for the genesis and progression of these tumors.