Influence of p53 mutations on prognosis of patients with glioblastoma

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Abstract
BACKGROUND: The influence of p53 mutations on the biology of astrocytic tumors is controversial. p53 is thought to be inactivated in the early stage of gliomagenesis; however, what role its inactivation plays in the malignancy of gliomas remains unknown. To understand the significance of p53 inactivation, the authors identified the locus of p53 gene mutation in glioma samples at different stages of progression and studied the correlation between the mutation and clinical behavior.METHODS: Samples from newly diagnosed gliomas, including pure and mixed astrocytomas, were analyzed for p53 mutations using a yeast functional assay. To determine the locus of the gene mutations, DNA sequencing was performed.RESULTS: The incidence of p53 mutations was higher in anaplastic astrocytomas (AA, 48%) than glioblastomas (GBM, 31%). There was no significant difference in the average ages of GBM patients with and without p53 mutations (54.9 years ± 2.3 and 53.2 years ± 4.6, respectively). In GBM patients, the mutation did not affect progression free survival or overall survival. Astrocytomas and GBM differed in the distribution of p53 mutation loci.CONCLUSIONS: The p53 gene mutation does not markedly affect the survival of GBM patients. The difference in the location of p53 mutations between AA and GBM suggests that in gliomas, the p53 mutation may contribute not only to tumorigenesis (as an early event) but also to progression to malignancy (as a late event). Cancer 2002;95:249–57. © 2002 American Cancer Society.DOI 10.1002/cncr.10677