Background: Mutations of the p53 gene are thought to be causally associated with the development of various neoplasms. In tumors overexpressing the wild-form of p53, its functional inactivation has been suggested, and MDM2 seems to be important in this process. We analyzed p53 in childhood solid tumors, as data on pediatric malignancies are still limited.
Procedure: The p53 gene was screened for mutations by the PCR-S SCP method and sequencing. p53, p21, and MDM2 proteins were analyzed by Western blotting.
Results: Overall, p53 mutations were found at a low frequency, 7% (9/126); the frequency calculated for sarcomas was also low, 8.6%. Interestingly, three of the nine detected mutations were new ones. p53 protein was demonstrated in all tumor histotypes, overall, in 63% (43/68) of the tumors, with 18% showing marked overexpression. No p21 was found; and the 76 kDa MDM2 protein was demonstrated in 18% (6/33) of the sarcomas.
Conclusions: In the series of pediatric malignancies studied, the frequency of p53 mutations was very low, whereas p53 protein was present in a high fraction of the tumors. Thus, in total, p53 abnormalities were frequent.
Copyright 2003 Wiley-Liss, Inc.