P53 mutations in Ewing's sarcoma

The p53 tumor suppressor gene is one of the most frequently altered genes i n human malignancies. To explore the implication of p53 alteration in Ewing 's sarcoma, we analyzed the deletion and sequence alterations of p53 and ab normal amplification of MDM2, which acts as a functional inhibitor of p53, in 35 tissue specimens. Quantitative genomic PCR analysis showed that 2 of 35 tumors have extremely low levels of the p53 gene, indicating a homozygou s deletion of the gene. Mutational analysis of exons 4 to 9 of p53 by PCR-S SCP revealed that 3 of 35 tumors carry sequence alterations in exons 5 or 8 , and DNA sequencing analysis identified missense point mutations at codon 132 (AAG-ATG, lysine-methionine) and codon 135 (TGC --> TCC, cystein --> se rine) in exon 5, and codon 287 (GAG --> GTG, glutamic acid-valine) in exon 8 from these tumors. No abnormal amplification of the MDM2 gene was recogni zed. Taken together, our data demonstrate that p53 is genetically altered i n a small fraction of Ewing's sarcoma.