If. Pollack et al., Age and TP53 mutation frequency in childhood malignant gliomas: Results ina multi-institutional cohort, CANCER RES, 61(20), 2001, pp. 7404-7407
Malignant astrocytoma is one of the most deadly primary central nervous sys
tem tumors. Although significant progress has been made in understanding th
e molecular pathways that lead to the development of these tumors in adults
, comparatively little analysis has been done in childhood astrocytomas, wh
ich are less common and have a more favorable prognosis. Our previous studi
es of an institutional cohort of children with malignant gliomas suggested
the existence of distinct molecular pathways of tumorigenesis in younger ve
rsus older children, based on the finding of a high frequency of TP53 mutat
ions in tumors from children > 3 years of age at diagnosis, compared with t
hose from younger children. In the current study, the association between T
P53 mutations and age was examined in greater detail using the multi-instit
utional group of children enrolled in Children's Cancer Group Study 945, th
e largest cohort of childhood high-grade gliomas analyzed to date. Seventy-
seven tumors with centrally reviewed diagnoses of anaplastic astrocytoma or
glioblastoma multiforme had sufficient archival histopathological material
for microdissection-based genotyping. Sections were examined histologicall
y, and topographic targets that contained malignant tissue were isolated by
microdissection and subjected to PCR-based amplification and sequencing of
TP53 exons 5-8. Twenty-six tumors (33.8%) had mutations in those exons. Mu
tations were observed in 2 of 17 tumors (11.8%) from children < 3 years of
age at diagnosis versus 24 of 60 tumors (40%) from older children, a differ
ence that was statistically significant (P = 0.04), in agreement with our p
revious results. Whereas malignant gliomas in older children have a frequen
cy of mutations comparable to tumors that arise in young adults, those from
children < 3 years old do not. The association between age and frequency o
f TP53 mutations among pediatric malignant gliomas indicates the probable e
xistence of two distinct pathways of molecular tumorigenesis in younger ver
sus older children.