title: P53 mutations in Ewing's sarcoma.
abstract: The p53 tumor suppressor gene is one of the most frequently altered genes in human malignancies. To explore the implication of p53 alteration in Ewing's sarcoma, we analyzed the deletion and sequence alterations of p53 and abnormal 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 homozygous deletion of the gene. Mutational analysis of exons 4 to 9 of p53 by PCR-SSCP 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-->serine) 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 recognized. Taken together, our data demonstrate that p53 is genetically altered in a small fraction of Ewing's sarcoma.
authors: Department of Pathology, Kyung Hee University Hospital, Dongdaemoon-gu, Seoul 130-702, Korea. ykpark@khmc.or.kr
authors: Y K
authors: YK
authors: Park
authors: S G
authors: SG
authors: Chi
authors: Y W
authors: YW
authors: Kim
authors: H R
authors: HR
authors: Park
authors: K K
authors: KK
authors: Unni
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D009687:Nuclear Proteins; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011471:Prostatic Neoplasms / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2