High frequency of TP53 mutations in juvenile pilocytic astrocytomas indicates role of TP53 in the development of these tumors.

Abstract

In adults, the TP53 tumor suppressor gene is frequently mutated in astrocytic brain tumors which is supposed to represent an early event in their development. In juvenile pilocytic and low-grade astrocytomas, however, TP53 mutations have until now been reported as rare, which has led to the suggestion that these tumors may follow a different molecular pathogenesis with an involvement of genes other than TP53. Our analysis of 20 pilocytic and two low-grade astrocytomas of childhood, based on a comprehensive denaturing gradient gel electrophoresis (DGGE) mutation detection assay of the entire coding region, including all splice site junctions of TP53, showed mutations considered as causative in 7 of the 20 (35%) pilocytic astrocytomas and in one of the two low-grade astrocytomas. Our finding is significantly different from the mutation frequency of 1.3% (2/155) previously reported for these tumor types. This may be attributed to the mutation detection system used, which also detects mutations occurring outside the evolutionary conserved region of TP53. Our results suggest that, contrary to the present notion, TP53 mutations may well play a role in the development of juvenile astrocytomas. Furthermore, no mutations were found in tumors of patients with progression of residual tumor after postoperative follow-up. This suggests that TP53 mutations may be associated with less aggressive forms of juvenile astrocytomas, analogous to the situation in adult astrocytomas.