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p53 and ras mutations in Ewing's sarcoma
K Radig1, R Schneider-Stock, I Röse
1Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany.
Abstract:
The role of tumor suppressor genes and oncogenes in the development of Ewing's sarcoma has not yet been fully clarified. In this study, we analyzed the frequency of p53 tumor suppressor gene mutation in exons 4-8 by PCR-SSCP and direct sequencing, and the expression of p53-protein in Ewing's sarcoma (ES) by using immunohistochemistry. The overexpression of MDM2, which acts as a functional inactivator of p53, was studied by immunohistochemistry. In addition, a screening for point mutations in the hot spot regions codon 12 and 13 of exon 1 and codon 61 of exon 2 of ras-genes (H-ras, N-ras, K-ras) was performed. In one case, a p53 gene mutation could be confirmed in codon 238 of exon 7 (1/24). Overexpression of MDM2 was found in five cases; in ras-genes, no mutations were detected. Compared with other highly malignant mesenchymal pediatric tumors such as osteosarcomas, mutations of p53 and ras in Ewing's sarcomas are an extraordinarily rare event. However, their frequency is comparable to that of PNET, suggesting that the low incidence of these mutations in ES and PNET could be group-specific for tumors of neuroectodermal genesis.
Insights
Tumor suppressor gene mutations are rare in Ewing sarcoma (ES). This study found p53 gene mutations in only one case and no ras gene mutations, suggesting a group-specific characteristic for neuroectodermal tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The roles of tumor suppressor genes and oncogenes in Ewing sarcoma (ES) development require further clarification.
- Understanding these genetic alterations is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the frequency of p53 tumor suppressor gene mutations and p53-protein expression in ES.
- To analyze MDM2 overexpression, a functional p53 inactivator.
- To screen for mutations in hot spot regions of ras-genes (H-ras, N-ras, K-ras).
Main Methods:
- Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing for p53 gene mutation analysis.
- Immunohistochemistry to assess p53-protein and MDM2 expression.
- Screening for point mutations in ras-genes.
Main Results:
- A p53 gene mutation was identified in one out of 24 ES cases (codon 238, exon 7).
- MDM2 overexpression was observed in five cases.
- No mutations were detected in the screened ras-genes.
- Mutations in p53 and ras genes are rare in ES compared to osteosarcomas.
Conclusions:
- The low incidence of p53 and ras mutations in ES is comparable to PNET (primitive neuroectodermal tumors).
- This suggests a potential group-specific characteristic for tumors of neuroectodermal origin.
- Further research into the genetic landscape of ES is warranted.