Tumours of the astrocytic series (H&E). (A) Astrocytoma malignancy grade II (arrows pointing to thin walled tumour capillary vessels). (B) Anaplastic astrocytoma malignancy grade III demonstrating anaplastic tumour cells but with no evidence for microvascular proliferation (arrows; compare with A and C). (C) Glioblastoma with florid endothelial proliferation (arrows).
Before reading the following section it is essential that fig 5 is first reviewed and referred to as necessary. Cytogenetic and molecular data are limited on astrocytomas (malignancy grade II) as they are not so common. Over 60% of astrocytomas (malignancy grade II) have loss of alleles on 17p, including the TP53 locus, and the retained TP53 allele is mutated in the majority of cases.
The absence of wild type p53 is therefore the most common abnormal finding in astrocytomas malignancy grade II, resulting in a non-functional p53 pathway. A small percentage of tumours have mutations of one allele but retain one wild type allele. As the p53 protein is believed to function as a tetramer and as tetramers with one abnormal p53 protein may not function normally, the finding of these single mutated alleles together with a wild type allele may well be significant.
Other genes coding for components of the p53 pathway (fig 5), MDM2 and p14ARF, have been studied in small numbers of these tumours and no abnormalities have been reported. Recent studies of the TP53 related gene, P73, have not identified any mutations. Other findings considered significant include overexpression of the PDGFRA gene. Loss of alleles from 6q, 13q, and 22q occur in some astrocytomas.
There is no evidence to suggest that there is mutation of the single retained tumour suppressor gene RB1 allele at 13q14.2 or the NF2 tumour suppressor gene on 22q. Deletion mapping of chromosomes 6 shows losses on 6q in a significant number of astrocytomas.
The potential tumour suppressor genes in all of these regions remain unknown. There are no consistently reported amplified genes or amplified regions of the genome in astrocytomas. The changes found in the astrocytomas form the baseline for progression in the adult diffuse astrocytic tumour series. Epigenetic changes such as hypermethylation of tumour suppressor gene promoters may also play an important role in transcriptional silencing of some of the genes cited above or other important cancer genes and the development of astrocytomas.
