A subpopulation of cells were present in the low-grade tumours that contained the same p53 gene mutation predominant in the cells of the recurrent tumours that had progressed to glioblastoma.
The more malignant histological features of anaplastic astrocytoma and glioblastoma multiforme appear to be reflected by a greater incidence of p53 accumulation.
LOH on chromosome 10 and p53 mutation were found together only in patients with glioblastoma multiforme (22%), suggesting that these genetic changes may accumulate during astrocytoma progression.
Our results show that p53 mutations are not restricted to glioblastoma multiforme and may be important in the tumorigenesis of lower-grade astrocytomas and that p53 mutations in lower-grade astrocytomas are associated with loss of chromosome 17p.
Human malignant gliomas (glioblastomas and anaplastic astrocytomas) are the most frequent brain tumors and are associated with a variety of genetic alterations including retinoblastoma (RB) and p53 gene mutations, loss of interferon alpha and beta (IFNA, IFNB) genes and lack of O6-methylguanine-DNA methyltransferase (MGMT) expression.
Results suggested that aberrations of the p53 gene were not correlated with the malignancy of some types of brain tumors such as anaplastic astrocytoma and glioblastoma, contrary to previous observations on colorectal cancers.
Five of the remaining 40 cases (12.5%) showed allelic imbalance at the p53 locus (three anaplastic astrocytomas [grade III] and two glioblastomas [grade IV]).
We have investigated the increased levels of p53 and hsp72 after UV or gamma-ray irradiation and the association of these using two human glioblastoma cell lines.
This case report describes the use of allele-specific PCR (A-PCR) to detect a C-->T transition in p53 codon 273 in DNA extracted from the cerebrospinal fluid (CSF) of a patient whose glioblastoma contained the same mutation.
In this study, we show that the expression of both wild-type p53 and MDM2 (murine double minute 2) proteins was induced when cis-diamminedichloroplatinum (cisplatin) caused apoptosis in human glioblastoma U87-MG cells, which expressed neither wild-type p53 nor MDM2 protein prior to treatment.
To assess the functional significance of these mutations, wild-type (WT) p53 genes were introduced into glioblastoma cell lines having mutant, WT, or null endogenous p53 alleles.
When compared with the histological grading, the rates of OS for Tel 17p and p53 in anaplastic astrocytomas were higher than those of glioblastomas, suggesting that the deletion may be associated with the early events in tumorigenesis and that some glioblastomas without chromosome 17 aberrations may be independent from tumour progression via low-grade gliomas.
Using a monoclonal antibody that reacts with both mutant and wild-type p53 protein (PAb 1801), reactivity was assessed immunohistochemically in specimens from the first diagnosis of astrocytic neoplasm in 95 patients: 26 astrocytomas (A), 19 anaplastic astrocytomas (AA), and 50 glioblastomas multiforme (GBM).
These findings suggest that histologically indistinguishable, low-grade astrocytic gliomas that are destined to progress to higher grades, do so along two distinct clinicopathologic pathways (either stepwise to anaplastic glioma, then glioblastoma, or directly to glioblastoma) marked by the presence or absence of p53 mutation.
We evaluated 35 astrocytic tumors (17 pilocytic, 4 diffuse low grade, 12 anaplastic, and 2 glioblastoma) in pediatric patients for p53 mutations, using polymerase chain reaction-single-stranded conformation polymorphism analysis as a screening technique.