Abstract
Epidemiological studies on intracranial tumors have suggested that the observed familial aggregation of a proportion of gliomas may be due to inherited predisposition to their development. In the Li‐Fraumeni syndrome (LFS) associated with germ‐line mutations of the p53 gene, nervous‐system tumors are observed with increased frequency. However, the contribution of germ‐line p53 mutation to the incidence of brain tumors has not been investigated. In order to address this point, we have performed 2 independent investigations. First, we have examined an unselected series of brain tumors. Whenever the presence of a p53 mutation in the tumor was observed, the possible germ‐line origin of the mutation was investigated. Germ‐line p53 mutations were also analyzed in constitutional DNA of patients with gliomas that had been selected for an unusual personal or familial history of cancer. Germ‐line p53 mutations were detected in 1 out of 80 unselected cases and in 3 out of 15 selected cases (20%). We conclude that germ‐line p53 mutation may contribute to a small fraction of gliomas that develop in the general population. The presence of a personal or familial history of cancer in a patient with glioma should prompt the search for a germ‐line p53 mutation. However, the low frequency of p53 germ‐line mutation suggests that alterations of this gene may not account for most familial cases of gliomas. © 1995 Wiley‐Liss, Inc.