NARROW SPECTRUM OF INFREQUENT P53 MUTATIONS AND ABSENCE OF MDM2 AMPLIFICATION IN EWING TUMORS

The p53 and MDM2 genes are part of a physiological pathway frequently impaired in human cancer. With the exception of tumours occasionally a ssociated with hereditary predisposition, childhood malignancies have not been studied in detail vet. This is the first report on the analys is of p53 and MDM2 in a group of non-hereditary paediatric neoplasms r eferred to as the Ewing tumours (ETs). Thirty-seven primary tumours an d cell lines from 19 patients were screened for the presence of p53 mu tations. Only 5% of the primary tumour specimens were found to carry a n alteration within this gene. However, p53 mutations were 10-fold enr iched in ET cell lines, thus indicating a selective growth advantage i n vitro. Strikingly, five out of nine alterations detected were missen se mutations within codon 273, which were previously reported to impai r only partially the normal p53 function. Two single-base substitution s occurred at codons 277 and 176, and two alterations were loss-of-fun ction mutations. Investigation of the MDM2 gene revealed neither gene amplification in the primary tumours and cell lines nor significant ov erexpression in any of the cell lines. Our data therefore suggest that impairment of cellular mechanisms involving p53 is rare in a distinct group of childhood malignancies.