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MDM2 and CDK4 gene amplification in Ewing's sarcoma
M Ladanyi1, R Lewis, S C Jhanwar
1Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
The Journal of Pathology
|February 1, 1995
Summary
MDM2 gene amplification was found in 10% of Ewing
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MDM2 gene amplification, a known mechanism for p53 inactivation, is observed in various sarcomas.
- Alterations in the p53 pathway are not extensively studied in Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET).
Purpose of the Study:
- To investigate MDM2 gene amplification in ES and PNET.
- To explore the association between MDM2 amplification and clinical stage in these tumor types.
Main Methods:
- Southern blot analysis was used to detect MDM2 gene amplification in 30 ES/PNET specimens and 2 cell lines.
- EWS gene rearrangement was confirmed in all clinical specimens.
- CDK4 co-amplification was assessed.
Main Results:
- MDM2 gene amplification was detected in 3 out of 30 (10%) specimens (2 ES, 1 PNET), but not in cell lines.
- Two of the three amplified cases showed co-amplification of the CDK4 gene.
- MDM2 amplification was significantly associated with metastatic disease at diagnosis (P = 0.005).
Conclusions:
- MDM2 gene amplification occurs in a subset of ES and PNET.
- MDM2 amplification may be linked to advanced stage and metastatic potential in these sarcomas.