Vm. Hayes et al., High frequency of TP53 mutations in juvenile pilocytic astrocytomas indicates role of TP53 in the development of these tumors, BRAIN PATH, 9(3), 1999, pp. 463-467
In adults, the TP53 tumor suppressor gene is frequently mutated in astrocyt
ic brain tumors which is supposed to represent an early event in their deve
lopment. In juvenile pilocytic and low-grade astrocytomas, however, TP53 mu
tations have until now been reported as rare, which has led to the suggesti
on 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 gr
adient gel electrophoresis (DGGE) mutation detection assay of the entire co
ding 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 differe
nt from the mutation frequency of 1.3% (2/155) previously reported for thes
e 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 astrocyt
omas. Furthermore, no mutations were found in tumors of patients with progr
ession of residual tumor after postoperative follow-up. This suggests that
TP53 mutations may be associated with less aggressive forms of juvenile ast
rocytomas, analogous to the situation in adult astrocytomas.