MDM2 and CDK4 gene amplification in Ewing's sarcoma Journal Article
| Authors: | Ladanyi, M.; Lewis, R.; Jhanwar, S. C.; Gerald, W.; Huvos, A. G.; Healey, J. H. |
| Article Title: | MDM2 and CDK4 gene amplification in Ewing's sarcoma |
| Abstract: | Amplification of the MDM2 gene, which maps to chromosome band 12q13 and encodes a p53‐binding protein, may result in functional inactivation of p53 and has been observed in various bone and soft tissue sarcomas. Published studies have included few cases of Ewing's sarcoma (ES) or peripheral neuroectodermal tumour (PNET), a tumour group in which alterations of the p53 pathway have so far not been extensively studied. We examined two ES cell lines, RD‐ES and SK‐ES‐1, and 30 specimens from 27 patients (24 ES, 6 PNET; 19 primary, 4 local recurrence, 7 metastasis) for MDM2 gene amplification by Southern blot analysis. All 30 clinical specimens had been confirmed to contain sufficient ES/PNET DNA by the demonstration of a rearrangement of the t(11;22)‐associated EWS gene using an EWS cDNA probe on the same blots. MDM2 gene amplification was detected in 3 of 30 specimens (10 per cent), including two ES and one PNET, but in neither of the cell lines. The three cases with amplification were morphologically typical primary tumours. Two of the three cases also showed co‐amplification of the CDK4 gene, which endoces a cyclin‐dependent kinase and also maps to band 12q13. Clinically, all three cases had metastatic disease at diagnosis, compared with only 1 of 15 MDM2‐negative cases where the primary tumour was studied. The difference was statistically significant (P=0.005), suggesting an association of MDM2 amplification with advanced stage. Further accural and multivariate analysis of ES/PNET cases with MDM2 gene amplification will be necessary to confirm the clinical significance of these findings. The results suggest that the prevalence of MDM2 gene amplification in ES/PNET is comparable to other sarcomas, and implicate dysfunction of the p53 pathway in a subset of ES/PNET. The biological significance of CDK4 co‐amplification remains to be determined. Copyright © 1995 John Wiley & Sons, Ltd. |
| Keywords: | adolescent; adult; child; clinical article; controlled study; human tissue; bone neoplasms; child, preschool; proto-oncogene proteins; gene amplification; tumor cells, cultured; protein p53; ewing sarcoma; gene expression regulation, neoplastic; sarcoma, ewing's; neuroectoderm tumor; p53; neuroectodermal tumors, primitive, peripheral; mdm2; southern blotting; ewing's sarcoma; cdk4; blotting, southern; human; male; female; priority journal; article; support, non-u.s. gov't; peripheral neuroectodermal tumour |
| Journal Title: | Journal of Pathology |
| Volume: | 175 |
| Issue: | 2 |
| ISSN: | 0022-3417 |
| Publisher: | Wiley Blackwell |
| Date Published: | 1995-02-01 |
| Start Page: | 211 |
| End Page: | 217 |
| Language: | English |
| DOI: | 10.1002/path.1711750209 |
| PUBMED: | 7738717 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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