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P53 mutations in Ewing's sarcoma
1Department of Pathology, Kyung Hee University Hospital, Dongdaemoon-gu, Seoul 130-702, Korea. ykpark@khmc.or.kr
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.
Insights
Genetic alterations in the p53 tumor suppressor gene were investigated in Ewing's sarcoma. P53 gene mutations and deletions were identified in a small fraction of these rare pediatric tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p53 tumor suppressor gene is crucial in preventing cancer and is frequently altered in human malignancies.
- Understanding p53 alterations in rare pediatric cancers like Ewing's sarcoma is vital for therapeutic strategies.
Purpose of the Study:
- To investigate the frequency and nature of p53 gene alterations, including deletions and mutations, in Ewing's sarcoma.
- To assess the amplification of MDM2, a known inhibitor of p53, in these tumors.
Main Methods:
- Analysis of 35 Ewing's sarcoma tissue specimens.
- Quantitative genomic PCR for p53 deletion analysis.
- PCR-Single Strand Conformation Polymorphism (PCR-SSCP) and DNA sequencing for p53 mutational analysis.
- Analysis of MDM2 gene amplification.
Main Results:
- Homozygous deletion of the p53 gene was observed in 2 out of 35 tumors.
- Sequence alterations, including missense point mutations in exons 5 and 8, were found in 3 out of 35 tumors.
- No abnormal amplification of the MDM2 gene was detected in the analyzed specimens.
Conclusions:
- Genetic alterations of the p53 gene occur in a small subset of Ewing's sarcoma.
- These findings contribute to the understanding of the molecular pathogenesis of Ewing's sarcoma.