Influence of p53 mutations on prognosis of patients with glioblastoma.
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).
Department of Neurosurgery, Kumamoto University Medical School, Kumamoto, Japan. sshira@fc.kumamoto-u.ac.jp
Shoji
S
Shiraishi
Kenji
K
Tada
Hideo
H
Nakamura
Keishi
K
Makino
Masato
M
Kochi
Hideyuki
H
Saya
Jun-ichi
J
Kuratsu
Yukitaka
Y
Ushio
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics / Q000401:mortality; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D017422:Sequence Analysis, DNA; D015996:Survival Rate